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{{Short description|Biomolecule consisting of chains of amino acid residues}}
{{About|a class of molecules|protein as a nutrient|Protein (nutrient)|other uses|Protein (disambiguation)}}
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{{Good article}}
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[[File:Myoglobin.png|thumb|A representation of the 3D structure of the protein [[myoglobin]] showing turquoise [[alpha helix|α-helices]]. This protein was the first to have its structure solved by [[X-ray crystallography]]. Toward the right-center among the coils, a [[prosthetic group]] called a [[heme group]] (shown in gray) with a bound oxygen molecule (red).]]

'''Proteins''' are large [[biomolecule]]s and [[macromolecule]]s that comprise one or more long chains of [[amino acid]] [[residue (biochemistry)|residues]]. Proteins perform a vast array of functions within organisms, including [[Enzyme catalysis|catalysing metabolic reactions]], [[DNA replication]], [[Cell signaling|responding to stimuli]], providing [[Cytoskeleton|structure to cells]] and [[Fibrous protein|organisms]], and [[Intracellular transport|transporting molecules]] from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the [[Nucleic acid sequence|nucleotide sequence]] of their [[gene]]s, and which usually results in [[protein folding]] into a specific [[Protein structure|3D structure]] that determines its activity.

A linear chain of amino acid residues is called a [[polypeptide]]. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called [[peptide]]s. The individual amino acid residues are bonded together by [[peptide bond]]s and adjacent amino acid residues. The [[Protein primary structure|sequence]] of amino acid residues in a protein is defined by the [[DNA sequencing|sequence]] of a gene, which is encoded in the [[genetic code]]. In general, the genetic code specifies 20 standard amino acids; but in certain organisms the genetic code can include [[selenocysteine]] and—in certain [[archaea]]—[[pyrrolysine]]. Shortly after or even during synthesis, the residues in a protein are often chemically modified by [[post-translational modification]], which alters the physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Some proteins have non-peptide groups attached, which can be called [[prosthetic group]]s or [[Cofactor (biochemistry)|cofactors]]. Proteins can work together to achieve a particular function, and they often associate to form stable [[protein complex]]es.

Once formed, proteins only exist for a certain period and are then [[Proteolysis#Protein degradation|degraded]] and recycled by the cell's machinery through the process of [[protein turnover]]. A protein's lifespan is measured in terms of its [[half-life]] and covers a wide range. They can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal or misfolded proteins are degraded more rapidly either due to being targeted for destruction or due to being unstable.

Like other biological macromolecules such as [[polysaccharide]]s and [[nucleic acid]]s, proteins are essential parts of organisms and participate in virtually every process within [[cell (biology)|cells]]. Many proteins are [[enzyme]]s that [[catalysis|catalyse]] biochemical reactions and are vital to [[metabolism]]. Some proteins have structural or mechanical functions, such as [[actin]] and [[myosin]] in muscle, and the [[cytoskeleton]]'s scaffolding proteins that maintain cell shape. Other proteins are important in cell signaling, [[antibody|immune responses]], [[cell adhesion]], and the [[cell cycle]]. In animals, proteins are needed in the [[diet (nutrition)|diet]] to provide the [[essential amino acid]]s that cannot be [[amino acid synthesis|synthesized]]. [[Digestion]] breaks the proteins down for metabolic use.

==History and etymology==

{{further|History of molecular biology}}

=== Discovery and early studies ===

Proteins have been studied and recognized since the 1700s by [[Antoine François, comte de Fourcroy|Antoine Fourcroy]] and others,<ref name="Osborne-1909">{{cite book |author-link1=Thomas Burr Osborne (chemist) |title=The Vegetable Proteins |vauthors=Osborne TB |date=1909 |pages=1–6 |chapter=History |chapter-url=https://archive.org/details/vegetableprotein00osbouoft}}</ref><ref name="Reynolds2003" /> who often collectively called them "[[albumin]]s", or "albuminous materials" (''Eiweisskörper'', in German).<ref name="Reynolds2003" /> [[Gluten]], for example, was first separated from wheat in published research around 1747, and later determined to exist in many plants.<ref name="Osborne-1909" /> In 1789, Antoine Fourcroy recognized three distinct varieties of animal proteins: [[albumin]], [[fibrin]], and [[gelatin]].<ref>{{Cite book |last=Tanford |first=Charles |url=http://archive.org/details/naturesrobotshis0000tanf |title=Nature's robots: a history of proteins |date=2001 |publisher=Oxford; Toronto: Oxford University Press |others=Internet Archive |isbn=978-0-19-850466-5}}</ref> Vegetable (plant) proteins studied in the late 1700s and early 1800s included [[gluten]], [[Albumin|plant albumin]], [[gliadin]], and [[legumin]].<ref name="Osborne-1909" />

Proteins were first described by the Dutch chemist [[Gerardus Johannes Mulder]] and named by the Swedish chemist [[Jöns Jacob Berzelius]] in 1838.<ref name="Mulder1938">{{cite journal | vauthors = Mulder GJ | year = 1838 | url = https://archive.org/stream/bulletindesscien00leyd#page/104/mode/2up | title = Sur la composition de quelques substances animales | journal = Bulletin des Sciences Physiques et Naturelles en Néerlande | pages = 104 }}</ref><ref name="Hartley">{{cite journal | vauthors = Hartley H | title = Origin of the word 'protein' | journal = Nature | volume = 168 | issue = 4267 | pages = 244 | date = August 1951 | pmid = 14875059 | doi = 10.1038/168244a0 | s2cid = 4271525 | doi-access = free | bibcode = 1951Natur.168..244H }}</ref> Mulder carried out [[elemental analysis]] of common proteins and found that nearly all proteins had the same [[empirical formula]], C<sub>400</sub>H<sub>620</sub>N<sub>100</sub>O<sub>120</sub>P<sub>1</sub>S<sub>1</sub>.<ref name=Perrett2007/> He came to the erroneous conclusion that they might be composed of a single type of (very large) molecule. The term "protein" to describe these molecules was proposed by Mulder's associate Berzelius; protein is derived from the [[Greek language|Greek]] word {{lang|el|πρώτειος|italic=no}} ({{transliteration|el|proteios|italic=yes}}), meaning "primary",<ref>{{cite encyclopedia | encyclopedia = Oxford English Dictionary | title = Protein (n.) | date = July 2023 | doi = 10.1093/OED/5657543824 }}</ref> "in the lead", or "standing in front",<ref name=Reynolds2003/> + ''[[wikt:-in#Suffix|-in]]''. Mulder went on to identify the products of protein degradation such as the [[amino acid]] [[leucine]] for which he found a (nearly correct) molecular weight of 131 [[atomic mass unit|Da]].<ref name=Perrett2007/>

Early nutritional scientists such as the German [[Carl von Voit]] believed that protein was the most important nutrient for maintaining the structure of the body, because it was generally believed that "flesh makes flesh."<ref name=Bischoff1860/> Around 1862, [[Karl Heinrich Ritthausen]] isolated the amino acid [[glutamic acid]].<ref>{{cite journal |last1=Osborne |first1=Thomas B. |date=April 1913 |title=In Memoriam Heinrich Ritthausen |url=https://www.biodiversitylibrary.org/ia/blumenzeitung09hssl#page/400/mode/2up |journal=Biochemical Bulletin |publisher=[[Columbia University]] Biochemical Association |volume=II |page=338 |authorlink1=Thomas Burr Osborne (chemist) |accessdate=1 January 2016 |number=7}}, archived at the [[Biodiversity Heritage Library]]</ref> [[Thomas Burr Osborne (chemist)|Thomas Burr Osborne]] compiled a detailed review of the vegetable proteins at the [[Connecticut Agricultural Experiment Station]]. Osborne, alongside [[Lafayette Mendel]], established several [[essential amino acid|nutritionally essential amino acids]] in feeding experiments with laboratory rats.<ref>{{Cite journal |last1=Simoni |first1=Robert D. |last2=Hill |first2=Robert L. |last3=Vaughan |first3=Martha |date=2002-05-03 |title=Nutritional Biochemistry and the Amino Acid Composition of Proteins: the Early Years of Protein Chemistry. The Work of Thomas B. Osborne and Lafayette B. Mendel |journal=Journal of Biological Chemistry |volume=277 |issue=18 |pages=14–15 |doi=10.1016/S0021-9258(19)35800-4 |doi-access=free }}</ref> Diets lacking an essential amino acid stunts the rats' growth, consistent with [[Liebig's law of the minimum]].<ref>{{Cite journal |last1=Osborne |first1=Thomas B. |last2=Mendel |first2=Lafayette B. |last3=Ferry |first3=Edna L. |last4=Wakeman |first4=Alfred J. |date=1916 |title=The Amino-Acid Minimum for Maintenance and Growth, as Exemplified by Further Experiments with Lysine and Tryptophane |journal=Journal of Biological Chemistry |volume=25 |issue=1 |pages=1–12 |doi=10.1016/S0021-9258(18)87509-3 |doi-access=free }}</ref> The final essential amino acid to be discovered, [[threonine]], was identified by [[William Cumming Rose]].<ref>{{Cite journal |last1=Simoni |first1=Robert D. |last2=Hill |first2=Robert L. |last3=Vaughan |first3=Martha |date=2002-09-13 |title=The Discovery of the Amino Acid Threonine: the Work of William C. Rose |journal=Journal of Biological Chemistry |volume=277 |issue=37 |pages=56–58 |doi=10.1016/S0021-9258(20)74369-3 |doi-access=free }}</ref>

The difficulty in purifying proteins impeded work by early protein biochemists. Proteins could be obtained in large quantities from blood, egg whites, and [[keratin]], but individual proteins were unavailable.  In the 1950s, the [[Armour and Company|Armour Hot Dog Company]] purified 1&nbsp;kg of bovine pancreatic [[ribonuclease A]] and made it freely available to scientists.  This gesture helped ribonuclease A become a major target for biochemical study for the following decades.<ref name="Perrett2007" />

=== Polypeptides ===

[[File:Peptide bond.jpg|thumb|polypeptide]]

The understanding of proteins as [[polypeptide]]s, or chains of amino acids, came through the work of [[Franz Hofmeister]] and [[Hermann Emil Fischer]] in 1902.<ref>{{cite web|url=http://www.encyclopedia.com/science/dictionaries-thesauruses-pictures-and-press-releases/hofmeister-franz|title=Hofmeister, Franz|publisher=encyclopedia.com|access-date=4 April 2017|archive-url=https://web.archive.org/web/20170405073423/http://www.encyclopedia.com/science/dictionaries-thesauruses-pictures-and-press-releases/hofmeister-franz|archive-date=5 April 2017|url-status=live}}</ref><ref>{{cite web | vauthors = Koshland DE, Haurowitz F |url=https://www.britannica.com/science/protein/Conformation-of-proteins-in-interfaces#ref593795|title=Protein, section: Classification of protein|publisher=britannica.com|access-date=4 April 2017|archive-url=https://web.archive.org/web/20170404225132/https://www.britannica.com/science/protein/Conformation-of-proteins-in-interfaces#ref593795|archive-date=4 April 2017|url-status=live}}</ref> The central role of proteins as [[enzyme]]s in living organisms that catalyzed reactions was not fully appreciated until 1926, when [[James B. Sumner]] showed that the enzyme [[urease]] was in fact a protein.<ref name="Sumner1926" />

[[Linus Pauling]] is credited with the successful prediction of regular protein [[secondary structure]]s based on [[hydrogen bonding]], an idea first put forth by [[William Astbury]] in 1933.<ref name="Pauling1951" /> Later work by [[Walter Kauzmann]] on [[Denaturation (biochemistry)|denaturation]],<ref name="Kauzmann1956" /><ref name="Kauzmann1959" /> based partly on previous studies by [[Kaj Ulrik Linderstrøm-Lang|Kaj Linderstrøm-Lang]],<ref name="Kalman1955" /> contributed an understanding of [[protein folding]] and structure mediated by [[hydrophobic core|hydrophobic interactions]].<ref>{{Cite journal |last=Dill |first=Ken A. |date=1990 |title=Dominant forces in protein folding |url=https://pubs.acs.org/doi/abs/10.1021/bi00483a001 |journal=Biochemistry |volume=29 |issue=31 |pages=7133–7155 |doi=10.1021/bi00483a001|pmid=2207096 }}</ref>

The first protein to have its amino acid chain [[protein sequencing|sequenced]] was [[insulin]], by [[Frederick Sanger]], in 1949. Sanger correctly determined the amino acid sequence of insulin, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, [[colloid]]s, or [[cyclol]]s.<ref name=Sanger1949/> He won the Nobel Prize for this achievement in 1958.<ref name="Lecture 1958"/> [[Christian Anfinsen]]'s studies of the [[oxidative folding]] process of ribonuclease A, for which he won the nobel prize in 1972, solidified the [[thermodynamic hypothesis]] of protein folding, according to which the folded form of a protein represents its [[Free energy (thermodynamics)|free energy]] minimum.<ref name="pmid17754377">{{cite journal |vauthors=Richards FM |year=1972 |title=The 1972 nobel prize for chemistry |journal=Science |volume=178 |issue=4060 |pages=492–3 |bibcode=1972Sci...178..492R |doi=10.1126/science.178.4060.492 |pmid=17754377}}</ref><ref name="marshall">{{Cite journal |last1=Marshall |first1=G. R. |last2=Feng |first2=J. A. |last3=Kuster |first3=D. J. |year=2008 |title=Back to the future: Ribonuclease A |journal=Biopolymers |volume=90 |issue=3 |pages=259–77 |doi=10.1002/bip.20845 |pmid=17868092 |doi-access=free}}</ref>

=== Structure ===

[[File:KendrewMyoglobin.jpg|thumb|upright=1.15|[[John Kendrew]] with model of myoglobin in progress]]

With the development of [[X-ray crystallography]], it became possible to determine protein structures as well as their sequences.<ref name="Stoddart">{{cite journal | vauthors = Stoddart C |title=Structural biology: How proteins got their close-up |journal=Knowable Magazine |date=1 March 2022 |doi=10.1146/knowable-022822-1 |doi-access=free }}</ref> The first [[protein structure]]s to be solved were [[hemoglobin]] by [[Max Perutz]] and [[myoglobin]] by [[John Kendrew]], in 1958.<ref name=Muirhead1963/><ref name=Kendrew1958/> The use of computers and increasing computing power has supported the sequencing of complex proteins. In 1999, [[Roger Kornberg]] sequenced the highly complex structure of [[RNA polymerase]] using high intensity X-rays from [[synchrotrons]].<ref name="Stoddart"/>

Since then, [[cryo-electron microscopy]] (cryo-EM) of large [[Macromolecular Assembly|macromolecular assemblies]]<ref name=Zhou2008/> has been developed. Cryo-EM uses protein samples that are frozen rather than crystals, and [[electron microscopy|beams of electrons]] rather than X-rays. It causes less damage to the sample, allowing scientists to obtain more information and analyze larger structures.<ref name="Stoddart"/> Computational [[protein structure prediction]] of small protein [[structural domain]]s<ref name=Keskin2008/> has helped researchers to approach atomic-level resolution of protein structures.
{{As of|April 2024}}, the [[Protein Data Bank]] contains 181,018 X-ray, 19,809 [[Cryogenic electron microscopy|EM]] and 12,697 [[Protein nuclear magnetic resonance spectroscopy|NMR]] protein structures.<ref>{{cite web |url=https://www.rcsb.org/stats/summary |title=Summary Statistics |website=RCSB PDB |access-date=2024-04-20}}</ref>

== Classification ==

{{Main|Protein family|Gene Ontology|Enzyme Commission number}}

Proteins are primarily classified by sequence and structure, although other classifications are commonly used. Especially for enzymes the EC number system provides a functional classification scheme.<ref name="McDonald Tipton 2023">{{cite journal |last1=McDonald |first1=Andrew G. |last2=Tipton |first2=Keith F. |title=Enzyme nomenclature and classification: the state of the art |journal=The FEBS Journal |volume=290 |issue=9 |date=2023 |issn=1742-464X |doi=10.1111/febs.16274 |doi-access=free |pages=2214–2231 |pmid=34773359 }}</ref> Similarly, [[Gene Ontology|gene ontology]] classifies both genes and proteins by their biological and biochemical function, and by their intracellular location.<ref name="pmid17984083">{{cite journal | vauthors = ((The Gene Ontology Consortium)) | title = The Gene Ontology project in 2008 | journal = Nucleic Acids Research | volume = 36 | issue = Database issue | pages = D440–4 | date = January 2008 | pmid = 17984083 | pmc = 2238979 | doi = 10.1093/nar/gkm883 }}</ref>

Sequence similarity is used to classify proteins both in terms of evolutionary and functional similarity. This may use either whole proteins or [[protein domain]]s, especially in [[Protein domain#Multidomain proteins|multi-domain proteins]]. Protein domains allow protein classification by a combination of sequence, structure and function, and they can be combined in many ways. In an early study of 170,000 proteins, about two-thirds were assigned at least one domain, with larger proteins containing more domains (e.g. proteins larger than 600 [[amino acid]]s having an average of more than 5 domains).<ref>{{cite journal | vauthors = Ekman D, Björklund AK, Frey-Skött J, Elofsson A | title = Multi-domain proteins in the three kingdoms of life: orphan domains and other unassigned regions | journal = Journal of Molecular Biology | volume = 348 | issue = 1 | pages = 231–243 | date = April 2005 | pmid = 15808866 | doi = 10.1016/j.jmb.2005.02.007 }}</ref>

== Biochemistry ==

[[File:Peptide-Figure-Revised.png|thumb|upright=1.35|Chemical structure of the peptide bond (bottom) and the three-dimensional structure of a peptide bond between an [[alanine]] and an adjacent amino acid (top/inset). The bond itself is made of the [[CHON]] elements.]]
[[File:Mesomeric peptide bond.svg|thumb|upright=1.35|[[Resonance (chemistry)|Resonance]] structures of the [[peptide bond]] that links individual amino acids to form a protein [[polymer]]]]

{{Main|Biochemistry|Amino acid|Peptide bond}}

Most proteins consist of linear [[polymer]]s built from series of up to 20 [[Chirality (chemistry)#In biochemistry|<small>L</small>-α-]]amino acids. All [[proteinogenic amino acid]]s have a common structure where an [[alpha carbon|α-carbon]] is [[chemical bond|bonded]] to an [[amino]] group, a [[carboxyl]] group, and a variable [[side chain]]. Only [[proline]] differs from this basic structure as its side chain is cyclical, bonding to the amino group, limiting protein chain flexibility.<ref name=Nelson2005/> The side chains of the [[list of standard amino acids|standard amino acids]] have a variety of chemical structures and properties, and it is the combined effect of all amino acids that determines its three-dimensional structure and chemical reactivity.<ref name=Gutteridge2005/>

The amino acids in a polypeptide chain are linked by [[peptide bond]]s between amino and carboxyl group. An individual amino acid in a chain is called a ''residue,'' and the linked series of carbon, nitrogen, and oxygen atoms are known as the ''main chain'' or ''protein backbone.''<ref name = "Murray_2006">{{cite book | vauthors = Murray RF, Harper HW, Granner DK, Mayes PA, Rodwell VW |title=Harper's Illustrated Biochemistry |publisher=Lange Medical Books/McGraw-Hill |location=New York |year=2006 |isbn=978-0-07-146197-9}}</ref>{{rp|19}} The peptide bond has two [[resonance (chemistry)|resonance]] forms that confer some [[double-bond]] character to the backbone. The alpha carbons are roughly [[coplanar]] with the nitrogen and the carbonyl (C=O) group. The other two [[dihedral angle]]s in the peptide bond determine the local shape assumed by the protein backbone. One conseqence of the N-C(O) double bond character is that proteins are somewhat rigid.<ref name = "Murray_2006" />{{rp|31}} A polypeptide chain ends with a free amino group, known as the ''[[N-terminus]]'' or ''amino terminus,'' and a free carboxyl group, known as the ''[[C-terminus]]'' or ''carboxy terminus''.<ref name=Reusch2013MSU>{{Cite web|url=https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/protein2.htm|title=Peptides & Proteins|last=Reusch|first=William|date=5 May 2013|website=Michigan State University Department of Chemistry}}</ref> By convention, peptide sequences are written N-terminus to C-terminus, correlating with the order in which proteins are [[translation (biology)|synthesized by ribosomes]].<ref name=Reusch2013MSU/><ref>{{cite book | last = Stryer | first = Lubert | name-list-style = vanc | title = Biochemistry | edition = Fifth | publisher = [[W. H. Freeman and Company]] | year = 2002 | isbn = 0-7167-4684-0 | page = 826 }}</ref>

The words ''protein'', ''polypeptide,'' and ''[[peptide]]'' are a little ambiguous and can overlap in meaning. ''Protein'' is generally used to refer to the complete biological molecule in a stable [[tertiary structure|conformation]], whereas ''peptide'' is generally reserved for a short amino acid oligomers often lacking a stable 3D structure. But the boundary between the two is not well defined and usually lies near 20–30 residues.<ref name=Lodish2004/>

Proteins can interact with many types of molecules and ions, including [[protein–protein interaction|with other proteins]], [[Protein–lipid interaction|with lipids]], [[Protein–carbohydrate interaction|with carbohydrates]], and [[Protein–DNA interaction|with DNA]].<ref>{{cite journal | vauthors = Ardejani MS, Powers ET, Kelly JW | title = Using Cooperatively Folded Peptides To Measure Interaction Energies and Conformational Propensities | journal = Accounts of Chemical Research | volume = 50 | issue = 8 | pages = 1875–1882 | date = August 2017 | pmid = 28723063 | pmc = 5584629 | doi = 10.1021/acs.accounts.7b00195 }}</ref><ref name = "Brandon_1999">{{cite book |vauthors=Branden C, Tooze J |title=Introduction to Protein Structure |publisher=Garland Pub |location=New York |year=1999 |isbn=978-0-8153-2305-1}}</ref><ref name = "Van_Holde_1996">{{cite book |vauthors=Van Holde KE, Mathews CK |title=Biochemistry |publisher=Benjamin/Cummings |location=Menlo Park, California |year=1996 |isbn=978-0-8053-3931-4 |url=https://archive.org/details/biochemistry00math }}</ref>

=== Abundance in cells ===

A typical [[bacteria]]l cell, e.g. ''[[Escherichia coli|E. coli]]'' and ''[[Staphylococcus aureus]]'', is estimated to contain about 2 million proteins. Smaller bacteria, such as ''[[Mycoplasma]]'' or ''[[Spirochaete|spirochetes]]'' contain fewer molecules, on the order of 50,000 to 1 million. By contrast, [[Eukaryote|eukaryotic]] cells are larger and thus contain much more protein. For instance, [[Saccharomyces cerevisiae|yeast]] cells have been estimated to contain about 50 million proteins and [[human]] cells on the order of 1 to 3 billion.<ref>{{cite journal | vauthors = Milo R | title = What is the total number of protein molecules per cell volume? A call to rethink some published values | journal = BioEssays | volume = 35 | issue = 12 | pages = 1050–1055 | date = December 2013 | pmid = 24114984 | pmc = 3910158 | doi = 10.1002/bies.201300066 }}</ref> The concentration of individual protein copies ranges from a few molecules per cell up to 20 million.<ref name="pmid22068332">{{cite journal | vauthors = Beck M, Schmidt A, Malmstroem J, Claassen M, Ori A, Szymborska A, Herzog F, Rinner O, Ellenberg J, Aebersold R | title = The quantitative proteome of a human cell line | journal = Molecular Systems Biology | volume = 7 | pages = 549 | date = November 2011 | pmid = 22068332 | pmc = 3261713 | doi = 10.1038/msb.2011.82 }}</ref> Not all genes coding proteins are expressed in most cells and their number depends on, for example, cell type and external stimuli. For instance, of the 20,000 or so proteins encoded by the human genome, only 6,000 are detected in [[lymphoblastoid]] cells.<ref>{{cite journal | vauthors = Wu L, Candille SI, Choi Y, Xie D, Jiang L, Li-Pook-Than J, Tang H, Snyder M | title = Variation and genetic control of protein abundance in humans | journal = Nature | volume = 499 | issue = 7456 | pages = 79–82 | date = July 2013 | pmid = 23676674 | pmc = 3789121 | doi = 10.1038/nature12223 | bibcode = 2013Natur.499...79W }}</ref>  The most abundant protein in nature is thought to be [[RuBisCO]], an enzyme that catalyzes the incorporation of [[carbon dioxide]] into organic matter in [[photosynthesis]].  Plants can consist of as much as 1% by weight of this enzyme,<ref>{{cite journal |doi=10.1016/0968-0004(79)90212-3 |title=The most abundant protein in the world |date=1979 |last1=Ellis |first1=R.John |journal=Trends in Biochemical Sciences |volume=4 |issue=11 |pages=241–244 }}</ref>

==Synthesis==

===Biosynthesis===

[[File:Ribosome mRNA translation en.svg|thumb|A ribosome produces a protein using mRNA as template]]
[[File:Genetic code.svg|thumb|class=skin-invert-image|The [[DNA]] sequence of a gene [[genetic code|encodes]] the amino acid sequence of a protein]]

{{Main|Protein biosynthesis}}

Proteins are assembled from amino acids using information encoded in genes. Each protein has its own unique amino acid sequence that is specified by the [[nucleotide]] sequence of the gene encoding this protein. The [[genetic code]] is a set of three-nucleotide sets called [[codon]]s and each three-nucleotide combination designates an amino acid, for example AUG ([[adenine]]–[[uracil]]–[[guanine]]) is the code for [[methionine]]. Because [[DNA]] contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon.<ref name = "Van_Holde_1996" />{{rp|1002–42}} Genes encoded in DNA are first [[transcription (genetics)|transcribed]] into pre-[[messenger RNA]] (mRNA) by proteins such as [[RNA polymerase]]. Most organisms then process the pre-mRNA (a ''primary transcript'') using various forms of [[post-transcriptional modification]] to form the mature mRNA, which is then used as a template for protein synthesis by the [[ribosome]]. In [[prokaryote]]s the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the [[nucleoid]]. In contrast, [[eukaryote]]s make mRNA in the [[cell nucleus]] and then [[Protein translocation|translocate]] it across the [[nuclear membrane]] into the [[cytoplasm]], where [[protein biosynthesis|protein synthesis]] then takes place. The rate of protein synthesis is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second.<ref name=Pain2000/>

The process of synthesizing a protein from an mRNA template is known as [[translation (genetics)|translation]]. The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its [[base pair]]ing [[anticodon]] located on a [[transfer RNA]] molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme [[aminoacyl tRNA synthetase]] "charges" the tRNA molecules with the correct amino acids. The growing polypeptide is often termed the ''nascent chain''. Proteins are always biosynthesized from [[N-terminus]] to [[C-terminus]].<ref name = "Van_Holde_1996" />{{rp|1002–42}}

The size of a synthesized protein can be measured by the number of amino acids it contains and by its total [[molecular mass]], which is normally reported in units of ''daltons'' (synonymous with [[atomic mass unit]]s), or the derivative unit kilodalton (kDa). The average size of a protein increases from Archaea to Bacteria to Eukaryote (283, 311, 438 residues and 31, 34, 49 kDa respectively) due to a bigger number of [[protein domain]]s constituting proteins in higher organisms.<ref name="Kozlowski2016">{{cite journal | vauthors = Kozlowski LP | title = Proteome-pI: proteome isoelectric point database | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D1112–D1116 | date = January 2017 | pmid = 27789699 | pmc = 5210655 | doi = 10.1093/nar/gkw978 }}</ref> For instance, [[yeast]] proteins are on average 466 amino acids long and 53 kDa in mass.<ref name=Lodish2004/> The largest known proteins are the [[titin]]s, a component of the [[muscle]] [[sarcomere]], with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids.<ref name=Fulton1991/>

===Chemical synthesis===

{{main|Peptide synthesis}}

[[File:Peptide Synthesis.svg|thumb|Peptide Synthesis]]

Short proteins can be synthesized chemically by a family of [[peptide synthesis]] methods. These rely on [[organic synthesis]] techniques such as [[chemical ligation]] to produce peptides in high yield.<ref name=Bruckdorfer2004/> Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of [[fluorescent]] probes to amino acid side chains.<ref name=Schwarzer2005/> These methods are useful in laboratory [[biochemistry]] and [[cell biology]], though generally not for commercial applications. Chemical synthesis is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native [[tertiary structure]]. Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction.<ref name=Kent2009/>

== Structure ==

[[File:Chaperonin 1AON.png|thumb|right|upright=1.35|The crystal structure of the [[chaperonin]], a huge protein complex. A single protein subunit is highlighted. Chaperonins assist protein folding.]]
[[File:Proteinviews-1tim.png|thumb|upright=1.35|Three possible representations of the three-dimensional structure of the protein [[triose phosphate isomerase]]. '''Left''': All-atom representation colored by atom type. '''Middle:''' Simplified representation illustrating the backbone conformation, colored by secondary structure. '''Right''': Solvent-accessible surface representation colored by residue type (acidic residues red, basic residues blue, polar residues green, nonpolar residues white).]]

{{main|Protein structure}}

{{further|Protein structure prediction}}

Most proteins [[protein folding|fold]] into unique 3D structures. The shape into which a protein naturally folds is known as its [[native conformation]].<ref name = "Murray_2006" />{{rp|36}} Although many proteins can fold unassisted, simply through the chemical properties of their amino acids, others require the aid of molecular [[Chaperone (protein)|chaperones]] to fold into their native states.<ref name = "Murray_2006" />{{rp|37}} Biochemists often refer to four distinct aspects of a protein's structure:<ref name = "Murray_2006" />{{rp|30–34}}

* ''[[Primary structure]]'': the [[peptide sequence|amino acid sequence]]. A protein is a [[polyamide]].
* ''[[Secondary structure]]'': regularly repeating local structures stabilized by [[hydrogen bond]]s. The most common examples are the [[alpha helix|α-helix]], [[beta sheet|β-sheet]] and [[turn (biochemistry)|turns]]. Because secondary structures are local, many regions of distinct secondary structure can be present in the same protein molecule.
* ''[[Tertiary structure]]'': the overall shape of a single protein molecule; the spatial relationship of the secondary structures to one another. Tertiary structure is generally stabilized by nonlocal interactions, most commonly the formation of a [[hydrophobic core]], but also through [[Salt bridge (protein)|salt bridges]], hydrogen bonds, [[disulfide bond]]s, and even [[posttranslational modification|post-translational modification]]s. The term "tertiary structure" is often used as synonymous with the term ''fold''. The tertiary structure is what controls the basic function of the protein.
* ''[[Quaternary structure]]'': the structure formed by several protein molecules (polypeptide chains), usually called ''[[protein subunit]]s'' in this context, which function as a single [[protein complex]].
* ''[[Protein quinary structure|Quinary structure]]'': the signatures of protein surface that organize the crowded cellular interior. Quinary structure is dependent on transient, yet essential, macromolecular interactions that occur inside living cells.

Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "[[Chemical conformation|conformations]]", and transitions between them are called ''conformational changes.'' Such changes are often induced by the binding of a [[Substrate (biochemistry)|substrate]] molecule to an enzyme's [[active site]], or the physical region of the protein that participates in chemical catalysis. In solution, protein structures vary because of thermal vibration and collisions with other molecules.<ref name = "Van_Holde_1996" />{{rp|368–75}}

[[File:Protein composite.png|thumb|upright=1.35|Molecular surface of several proteins showing their comparative sizes. From left to right are: [[immunoglobulin G]] (IgG, an [[antibody]]), [[hemoglobin]], [[insulin]] (a hormone), [[adenylate kinase]] (an enzyme), and [[glutamine synthetase]] (an enzyme).]]

Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: [[globular protein]]s, [[fibrous protein]]s, and [[membrane protein]]s. Almost all globular proteins are [[soluble]] and many are enzymes. Fibrous proteins are often structural, such as [[collagen]], the major component of connective tissue, or [[keratin]], the protein component of hair and nails. Membrane proteins often serve as [[receptor (biochemistry)|receptors]] or provide channels for polar or charged molecules to pass through the [[cell membrane]].<ref name = "Van_Holde_1996" />{{rp|165–85}}

A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own [[dehydration]], are called [[dehydron]]s.<ref name=Fernandez2003/>

=== Protein domains ===

{{Main|Protein domain}}

Many proteins are composed of several [[protein domain]]s, i.e. segments of a protein that fold into distinct structural units.<ref name=Biochemistry2010>{{Cite book |last1=Garrett |first1=R. |title=Biochemistry |last2=Grisham |first2=Charles M. |date=2010 |publisher=Brooks/Cole, Cengage Learning |isbn=978-0-495-10935-8 |edition=4th |location=Belmont, CA}}</ref>{{rp|134}} Domains usually have specific functions, such as [[Enzyme|enzymatic]] activities (e.g. [[kinase]]) or they serve as binding modules.<ref name=Biochemistry2010 />{{rp|155–156}}

[[File:Domain organisation of EVH proteins.png|frame|'''Protein domains vs. motifs'''. Protein domains (such as the [[WH1 domain|EVH1 domain]]) are functional units within proteins that fold into defined 3D structures. Motifs are usually short sequences with specific functions but without a stable 3D structure. Many motifs are binding sites for other proteins (such as the red and green bars shown here in the context of a [[Ena/Vasp homology proteins|VASP]] protein).<ref>{{Cite journal |last1=Drees |first1=Frauke |last2=Gertler |first2=Frank B |date=2008-02-01 |title=Ena/VASP: proteins at the tip of the nervous system |journal=Current Opinion in Neurobiology |series=Development |volume=18 |issue=1 |pages=53–59 |doi=10.1016/j.conb.2008.05.007  |pmc=2515615 |pmid=18508258}}</ref>|center]]

=== Sequence motif ===
Short amino acid sequences within proteins often act as recognition sites for other proteins.<ref>{{cite journal | vauthors = Davey NE, Van Roey K, Weatheritt RJ, Toedt G, Uyar B, Altenberg B, Budd A, Diella F, Dinkel H, Gibson TJ | title = Attributes of short linear motifs | journal = Molecular BioSystems | volume = 8 | issue = 1 | pages = 268–281 | date = January 2012 | pmid = 21909575 | doi = 10.1039/c1mb05231d }}</ref> For instance, [[SH3 domain]]s typically bind to short PxxP motifs (i.e. 2 [[proline]]s [P], separated by two unspecified [[amino acid]]s [x], although the surrounding amino acids may determine the exact binding specificity). Many such motifs has been collected in the [[Eukaryotic Linear Motif resource|Eukaryotic Linear Motif]] (ELM) database.<ref>{{Cite journal |last1=Kumar |first1=Manjeet |last2=Gouw |first2=Marc |last3=Michael |first3=Sushama |last4=Sámano-Sánchez |first4=Hugo |last5=Pancsa |first5=Rita |last6=Glavina |first6=Juliana |last7=Diakogianni |first7=Athina |last8=Valverde |first8=Jesús Alvarado |last9=Bukirova |first9=Dayana |last10=Čalyševa |first10=Jelena |last11=Palopoli |first11=Nicolas |last12=Davey |first12=Norman E. |last13=Chemes |first13=Lucía B. |last14=Gibson |first14=Toby J. |date=2020-01-08 |title=ELM-the eukaryotic linear motif resource in 2020 |journal=Nucleic Acids Research |volume=48 |issue=D1 |pages=D296–D306 |doi=10.1093/nar/gkz1030 |pmc=7145657 |pmid=31680160}}</ref>

==Cellular functions==

Proteins are the chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes.<ref name=Lodish2004/> With the exception of certain types of [[RNA]], most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an ''[[Escherichia coli]]'' cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively.<ref name="Voet">Voet D, Voet JG. (2004). ''Biochemistry'' Vol 1 3rd ed. Wiley: Hoboken, NJ.</ref> The set of proteins expressed in a particular cell or cell type is known as its [[proteome]].<ref name=Biochemistry2010/>{{rp|120}}

[[File:Hexokinase ball and stick model, with substrates to scale copy.png|thumb|right|The enzyme [[hexokinase]] is shown as a conventional ball-and-stick molecular model. To scale in the top right-hand corner are two of its substrates, [[adenosine triphosphate|ATP]] and [[glucose]].]]

The chief characteristic of proteins that allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the [[binding site]] and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by the tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example, the [[ribonuclease inhibitor]] protein binds to human [[angiogenin]] with a sub-femtomolar [[dissociation constant]] (<10<sup>−15</sup> M) but does not bind at all to its amphibian homolog [[onconase]] (>&nbsp;1&nbsp;M). Extremely minor chemical changes such as the addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; for example, the [[aminoacyl tRNA synthetase]] specific to the amino acid [[valine]] discriminates against the very similar side chain of the amino acid [[isoleucine]].<ref name=Sankaranarayanan2001/>

Proteins can bind to other proteins as well as to [[Small molecule|small-molecule]] substrates. When proteins bind specifically to other copies of the same molecule, they can [[oligomer]]ize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. [[Protein–protein interaction]]s regulate enzymatic activity, control progression through the [[cell cycle]], and allow the assembly of large [[protein complex]]es that carry out many closely related reactions with a common biological function. Proteins can bind to, or be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows the construction of enormously complex [[cell signaling|signaling]] networks.<ref name = "Van_Holde_1996" />{{rp|830–49}}
As interactions between proteins are reversible and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function, study of the interactions between specific proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish particular cell types.<ref name=Copland2009/><ref name=Samarin2009/>

===Enzymes===

{{Main|Enzyme}}

The best-known role of proteins in the cell is as [[enzyme]]s, which [[catalysis|catalyse]] chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in [[metabolism]], as well as manipulating DNA in processes such as [[DNA replication]], [[DNA repair]], and [[transcription (genetics)|transcription]]. Some enzymes act on other proteins to add or remove chemical groups in a process known as posttranslational modification. About 4,000 reactions are known to be catalysed by enzymes.<ref name=EXPASY2000/> The rate acceleration conferred by enzymatic catalysis is often enormous—as much as 10<sup>17</sup>-fold increase in rate over the uncatalysed reaction in the case of [[orotate decarboxylase]] (78 million years without the enzyme, 18 milliseconds with the enzyme).<ref name=Radzicka1995/>

The molecules bound and acted upon by enzymes are called [[Substrate (biochemistry)|substrates]]. Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with the substrate, and an even smaller fraction—three to four residues on average—that are directly involved in catalysis.<ref name="urlEBI"/> The region of the enzyme that binds the substrate and contains the catalytic residues is known as the [[active site]].<ref name=Biochemistry2010/>{{rp|389}}

[[Dirigent protein]]s are members of a class of proteins that dictate the [[stereochemistry]] of a compound synthesized by other enzymes.<ref name="Pickel 2013"/>

===Cell signaling and ligand binding===

{{See also|Glycan-protein interactions}}

[[File:Mouse cholera antibody.png|thumb|upright|[[Ribbon diagram]] of a mouse antibody against [[cholera]] that binds a [[carbohydrate]] antigen]]

Many proteins are involved in the process of [[cell signaling]] and [[signal transduction]]. Some proteins, such as [[insulin]], are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant [[biological tissue|tissues]]. Others are [[membrane protein]]s that act as [[receptor (biochemistry)|receptors]] whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on the cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a [[conformational change]] detected by other proteins within the cell.<ref name = "Brandon_1999" />{{rp|251–81}}

[[Antibodies]] are protein components of an [[adaptive immune system]] whose main function is to bind [[antigen]]s, or foreign substances in the body, and target them for destruction. Antibodies can be [[secrete]]d into the extracellular environment or anchored in the membranes of specialized [[B cell]]s known as [[plasma cell]]s. Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high.<ref name = "Van_Holde_1996" />{{rp|275–50}}

Many ligand transport proteins bind particular [[Small molecule|small biomolecules]] and transport them to other locations in the body of a multicellular organism. These proteins must have a high binding affinity when their [[ligand]] is present in high concentrations, and release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is [[haemoglobin]], which transports [[oxygen]] from the [[lung]]s to other organs and tissues in all [[vertebrate]]s and has close homologs in every biological [[kingdom (biology)|kingdom]].<ref name = "Van_Holde_1996" />{{rp|222–29}} [[Lectins]] are [[Glycan-protein interactions|sugar-binding proteins]] which are highly specific for their sugar moieties. [[Lectins]] typically play a role in biological [[Molecular recognition|recognition]] phenomena involving cells and proteins.<ref name=Rudiger2000/> [[Receptor (biochemistry)|Receptors]] and [[hormone]]s are highly specific binding proteins.

[[Transmembrane protein]]s can serve as ligand transport proteins that alter the [[Semipermeable membrane|permeability]] of the cell membrane to [[small molecule]]s and ions. The membrane alone has a [[hydrophobic]] core through which [[Chemical polarity|polar]] or charged molecules cannot [[diffusion|diffuse]]. Membrane proteins contain internal channels that allow such molecules to enter and exit the cell. Many [[ion channel]] proteins are specialized to select for only a particular ion; for example, [[potassium]] and [[sodium]] channels often discriminate for only one of the two ions.<ref name = "Brandon_1999" />{{rp|232–34}}

===Structural proteins===

[[File:CHOP protein structure.png|thumb|Protein Structure]]

Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are [[fibrous protein]]s; for example, [[collagen]] and [[elastin]] are critical components of [[connective tissue]] such as [[cartilage]], and [[keratin]] is found in hard or filamentous structures such as [[hair]], [[nail (anatomy)|nails]], [[feather]]s, [[hoof|hooves]], and some [[Exoskeleton|animal shell]]s.<ref name = "Van_Holde_1996" />{{rp|178–81}} Some [[globular proteins]] can play structural functions, for example, [[actin]] and [[tubulin]] are globular and soluble as monomers, but [[polymer]]ize to form long, stiff fibers that make up the [[cytoskeleton]], which allows the cell to maintain its shape and size.<ref name=Biochemistry2010/>{{rp|490}}

Other proteins that serve structural functions are [[motor protein]]s such as [[myosin]], [[kinesin]], and [[dynein]], which are capable of generating mechanical forces. These proteins are crucial for cellular [[motility]] of single celled organisms and the [[spermatozoon|sperm]] of many multicellular organisms which reproduce [[Sexual reproduction|sexually]]. They generate the forces exerted by contracting [[muscle]]s<ref name = "Van_Holde_1996" />{{rp|258–64, 272}} and play essential roles in intracellular transport.<ref name=Biochemistry2010/>{{rp|481,490}}

==Methods of study==

{{Main|Protein methods}}

Methods commonly used to study protein structure and function include [[immunohistochemistry]], [[site-directed mutagenesis]], [[X-ray crystallography]], [[nuclear magnetic resonance]] and [[mass spectrometry]]. The activities and structures of proteins may be examined ''[[in vitro]],'' ''[[in vivo]], and [[in silico]]''. '''''In vitro''''' studies of purified proteins in controlled environments are useful for learning how a protein carries out its function:<ref>{{Citation |title=Experimental Animal and In Vitro Study Designs |vauthors=((National Research Council (US) Subcommittee on Reproductive and Developmental Toxicity)) |date=2001 |work=Evaluating Chemical and Other Agent Exposures for Reproductive and Developmental Toxicity |url=https://www.ncbi.nlm.nih.gov/books/NBK222201/ |access-date=2024-12-23 |publisher=National Academies Press}}</ref> for example, [[enzyme kinetics]] studies explore the [[reaction mechanism|chemical mechanism]] of an enzyme's catalytic activity and its relative affinity for various possible substrate molecules.<ref>{{Cite journal |last1=Ricard |first1=Jacques |last2=Cornish-Bowden |first2=Athel |date=July 1987 |title=Co-operative and allosteric enzymes: 20 years on |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1432-1033.1987.tb13510.x |journal=European Journal of Biochemistry |volume=166 |issue=2 |pages=255–272 |doi=10.1111/j.1432-1033.1987.tb13510.x|pmid=3301336 }}</ref> By contrast, '''''in vivo''''' experiments can provide information about the physiological role of a protein in the context of a [[Cell biology|cell]] or even a whole [[organism]], and can often provide more information about protein behavior in different contexts.<ref>{{Cite journal |last1=Lipinski |first1=Christopher |last2=Hopkins |first2=Andrew |date=December 2004 |title=Navigating chemical space for biology and medicine |url=https://www.nature.com/articles/nature03193 |journal=Nature |volume=432 |issue=7019 |pages=855–861 |doi=10.1038/nature03193|pmid=15602551 |bibcode=2004Natur.432..855L }}</ref> '''''In silico''''' studies use computational methods to study proteins.<ref>{{Cite journal |last1=Danchin |first1=A. |last2=Médigue |first2=C. |last3=Gascuel |first3=O. |last4=Soldano |first4=H. |last5=Hénaut |first5=A. |date=1991 |title=From data banks to data bases |url=https://linkinghub.elsevier.com/retrieve/pii/092325089190073J |journal=Research in Microbiology |volume=142 |issue=7–8 |pages=913–916 |doi=10.1016/0923-2508(91)90073-J|pmid=1784830 }}</ref>

===Protein purification===

{{Main|Protein purification}}

Proteins may be [[protein purification|purified]] from other cellular components using a variety of techniques such as [[ultracentrifugation]], [[Precipitation (chemistry)|precipitation]], [[electrophoresis]], and [[chromatography]];<ref name = "Murray_2006" />{{rp|21–24}} the advent of [[genetic engineering]] has made possible a number of methods to facilitate purification.<ref name=Terpe2003/>

To perform ''[[in vitro]]'' analysis, a protein must be purified away from other cellular components. This process usually begins with [[cytolysis|cell lysis]], in which a cell's membrane is disrupted and its internal contents released into a solution known as a [[crude lysate]]. The resulting mixture can be purified using [[ultracentrifugation]], which fractionates the various cellular components into fractions containing soluble proteins; membrane [[lipid]]s and proteins; cellular [[organelle]]s, and [[nucleic acid]]s. [[Precipitation (chemistry)|Precipitation]] by a method known as [[salting out]] can concentrate the proteins from this lysate. Various types of [[chromatography]] are then used to isolate the protein or proteins of interest based on properties such as molecular weight, net charge and binding affinity.<ref name = "Murray_2006" />{{rp|21–24}} The level of purification can be monitored using various types of [[gel electrophoresis]] if the desired protein's molecular weight and [[isoelectric point]] are known, by [[spectroscopy]] if the protein has distinguishable spectroscopic features, or by [[enzyme assay]]s if the protein has enzymatic activity. Additionally, proteins can be isolated according to their charge using [[electrofocusing]].<ref name=Hey2008/>

For natural proteins, a series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, [[genetic engineering]] is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity. Here, a "tag" consisting of a specific amino acid sequence, often a series of [[histidine]] residues (a "[[His-tag]]"), is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing [[nickel]], the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded. A number of tags have been developed to help researchers purify specific proteins from complex mixtures.<ref name=Terpe2003/>

===Cellular localization===

[[File:Localisations02eng.jpg|thumb|right|upright=1.35|Proteins in various [[cellular compartment]]s and structures tagged with [[green fluorescent protein]] (here, white)]]

The study of proteins ''in vivo'' is often concerned with the synthesis and localization of the protein within the cell. Although many intracellular proteins are synthesized in the [[cytoplasm]] and membrane-bound or secreted proteins in the [[endoplasmic reticulum]], the specifics of how proteins are [[protein targeting|targeted]] to specific organelles or cellular structures is often unclear. A useful technique for assessing cellular localization uses genetic engineering to express in a cell a [[fusion protein]] or [[chimera (protein)|chimera]] consisting of the natural protein of interest linked to a "[[reporter gene|reporter]]" such as [[green fluorescent protein]] (GFP).<ref name=Stepanenko2008/> The fused protein's position within the cell can then be cleanly and efficiently visualized using [[microscopy]].<ref name=Yuste2005/>

Other methods for elucidating the cellular location of proteins requires the use of known compartmental markers for regions such as the ER, the Golgi, lysosomes or vacuoles, mitochondria, chloroplasts, plasma membrane, etc. With the use of fluorescently tagged versions of these markers or of antibodies to known markers, it becomes much simpler to identify the localization of a protein of interest. For example, [[indirect immunofluorescence]] will allow for fluorescence colocalization and demonstration of location. Fluorescent dyes are used to label cellular compartments for a similar purpose.<ref name=Margolin2000/>

Other possibilities exist, as well. For example, [[immunohistochemistry]] usually uses an antibody to one or more proteins of interest that are conjugated to enzymes yielding either luminescent or chromogenic signals that can be compared between samples, allowing for localization information.<ref>{{Cite web |last=Hrycaj |first=Steven |date=17 October 2023 |title=Immunohistochemistry: Origins, Tips, and a Look to the Future |url=https://www.the-scientist.com/immunohistochemistry-origins-tips-and-a-look-to-the-future-71439 |access-date=2024-12-22 |website=The Scientist Magazine}}</ref> Another applicable technique is cofractionation in sucrose (or other material) gradients using [[isopycnic centrifugation]].<ref name=Walker2000/> While this technique does not prove colocalization of a compartment of known density and the protein of interest, it indicates an increased likelihood.<ref name=Walker2000/>

Finally, the gold-standard method of cellular localization is [[immunoelectron microscopy]]. This technique uses an antibody to the protein of interest, along with classical electron microscopy techniques. The sample is prepared for normal electron microscopic examination, and then treated with an antibody to the protein of interest that is conjugated to an extremely electro-dense material, usually gold. This allows for the localization of both ultrastructural details as well as the protein of interest.<ref name=Mayhew2008/>

Through another genetic engineering application known as [[site-directed mutagenesis]], researchers can alter the protein sequence and hence its structure, cellular localization, and susceptibility to regulation. This technique even allows the incorporation of unnatural amino acids into proteins, using modified tRNAs,<ref name=Hohsaka2002/> and may allow the rational [[protein design|design]] of new proteins with novel properties.<ref name=Cedrone2000/>

===Proteomics===

{{Main|Proteomics}}

The total complement of proteins present at a time in a cell or cell type is known as its [[proteome]], and the study of such large-scale data sets defines the field of [[proteomics]], named by analogy to the related field of [[genomics]]. Key experimental techniques in proteomics include [[Two-dimensional gel electrophoresis|2D electrophoresis]],<ref name=Gorg2008/> which allows the separation of many proteins, [[mass spectrometry]],<ref name=Conrotto2008/> which allows rapid high-throughput identification of proteins and sequencing of peptides (most often after [[in-gel digestion]]), [[protein microarray]]s, which allow the detection of the relative levels of the various proteins present in a cell, and [[two-hybrid screening]], which allows the systematic exploration of [[protein–protein interaction]]s.<ref name=Koegl2007/> The total complement of biologically possible such interactions is known as the [[interactome]].<ref name=Plewczynski2009/> A systematic attempt to determine the structures of proteins representing every possible fold is known as [[structural genomics]].<ref name=Zhang2003/>

===Structure determination===

Discovering the tertiary structure of a protein, or the quaternary structure of its complexes, can provide important clues about how the protein performs its function and how it can be affected, i.e. in [[Drug design#Structure-based|drug design]]. As proteins are [[Diffraction-limited system|too small to be seen]] under a [[Optical microscope|light microscope]], other methods have to be employed to determine their structure. Common experimental methods include [[X-ray crystallography]] and [[protein NMR|NMR spectroscopy]], both of which can produce structural information at [[atom]]ic resolution. However, NMR experiments are able to provide information from which a subset of distances between pairs of atoms can be estimated, and the final possible conformations for a protein are determined by solving a [[distance geometry]] problem. [[Dual polarisation interferometry]] is a quantitative analytical method for measuring the overall [[protein conformation]] and [[conformational change]]s due to interactions or other stimulus. [[Circular dichroism]] is another laboratory technique for determining internal β-sheet / α-helical composition of proteins. [[Cryoelectron microscopy]] is used to produce lower-resolution structural information about very large protein complexes, including assembled [[virus]]es;<ref name = "Brandon_1999" />{{rp|340–41}} a variant known as [[electron crystallography]] can produce high-resolution information in some cases, especially for two-dimensional crystals of membrane proteins.<ref name=Gonen2005/> Solved structures are usually deposited in the [[Protein Data Bank]] (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of [[Cartesian coordinates]] for each atom in the protein.<ref name=Standley2008/>

Many more gene sequences are known than protein structures. Further, the set of solved structures is biased toward proteins that can be easily subjected to the conditions required in [[X-ray crystallography]], one of the major structure determination methods. In particular, globular proteins are comparatively easy to [[crystallize]] in preparation for X-ray crystallography. Membrane proteins and large protein complexes, by contrast, are difficult to crystallize and are underrepresented in the PDB.<ref name=Walian2004/> [[Structural genomics]] initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. [[Protein structure prediction]] methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined.<ref name=Sleator2012/>

===Structure prediction===

[[File:225 Peptide Bond-01.jpg|thumb|right|upright=1.6|Constituent amino-acids can be analyzed to predict secondary, tertiary and quaternary protein structure, in this case hemoglobin containing [[heme]] units]]

{{Main|Protein structure prediction|List of protein structure prediction software}}

Complementary to the field of structural genomics, ''protein structure prediction'' develops efficient [[mathematical model]]s of proteins to computationally predict the molecular formations in theory, instead of detecting structures with laboratory observation.<ref name=Zhang2008/> The most successful type of structure prediction, known as [[homology modeling]], relies on the existence of a "template" structure with sequence similarity to the protein being modeled; structural genomics' goal is to provide sufficient representation in solved structures to model most of those that remain.<ref name=Xiang2006/> Although producing accurate models remains a challenge when only distantly related template structures are available, it has been suggested that [[sequence alignment]] is the bottleneck in this process, as quite accurate models can be produced if a "perfect" sequence alignment is known.<ref name=Zhang2005/> Many structure prediction methods have served to inform the emerging field of [[protein engineering]], in which novel protein folds have already been designed.<ref name=Kuhlman2003/> Many proteins (in eukaryotes ~33%) contain large unstructured but biologically functional segments and can be classified as [[intrinsically disordered proteins]]. Predicting and analysing protein disorder is an important part of protein structure characterisation.<ref>{{cite journal | vauthors = Ward JJ, Sodhi JS, McGuffin LJ, Buxton BF, Jones DT | title = Prediction and functional analysis of native disorder in proteins from the three kingdoms of life | journal = Journal of Molecular Biology | volume = 337 | issue = 3 | pages = 635–645 | date = March 2004 | pmid = 15019783 | doi = 10.1016/j.jmb.2004.02.002 | citeseerx = 10.1.1.120.5605 }}</ref>

===In silico simulation of dynamical processes===

A more complex computational problem is the prediction of intermolecular interactions, such as in [[docking (molecular)|molecular docking]],<ref name=Ritchie2008/> [[protein folding]], [[protein–protein interaction]] and chemical reactivity. Mathematical models to simulate these dynamical processes involve [[molecular mechanics]], in particular, [[molecular dynamics]]. In this regard, ''[[in silico]]'' simulations discovered the folding of small α-helical [[protein domain]]s such as the [[villin]] headpiece,<ref name=Zagrovic2002/> the [[HIV]] accessory protein<ref name=Herges2005/> and hybrid methods combining standard molecular dynamics with [[quantum mechanics|quantum mechanical]] mathematics have explored the electronic states of [[rhodopsin]]s.<ref name=Hoffman2006/>

Beyond classical molecular dynamics, [[quantum dynamics]] methods allow the simulation of proteins in atomistic detail with an accurate description of quantum mechanical effects. Examples include the multi-layer [[multi-configuration time-dependent Hartree ]] method and the [[hierarchical equations of motion]] approach, which have been applied to plant cryptochromes<ref name= Gatti2018/> and bacteria light-harvesting complexes,<ref name= Schulten2012/> respectively. Both quantum and classical mechanical simulations of biological-scale systems are extremely computationally demanding, so [[distributed computing]] initiatives such as the [[Folding@home]] project facilitate the [[molecular modeling on GPU|molecular modeling]] by exploiting advances in [[Graphics processing unit|GPU]] parallel processing and [[Monte Carlo method|Monte Carlo]] techniques.<ref name=Scheraga2007/><ref name="Zheng Javidpour 2020">{{cite journal |last1=Zheng |first1=Size |last2=Javidpour |first2=Leili |last3=Sahimi |first3=Muhammad |last4=Shing |first4=Katherine S. |last5=Nakano |first5=Aiichiro |title=sDMD: An open source program for discontinuous molecular dynamics simulation of protein folding and aggregation |journal=Computer Physics Communications |volume=247 |date=2020 |doi=10.1016/j.cpc.2019.106873 |page=106873|bibcode=2020CoPhC.24706873Z }}</ref>

===Chemical analysis===

The total nitrogen content of organic matter is mainly formed by the amino groups in proteins. The Total Kjeldahl Nitrogen ([[TKN]]) is a measure of nitrogen widely used in the analysis of (waste) water, soil, food, feed and organic matter in general. As the name suggests, the [[Kjeldahl method]] is applied. More sensitive methods are available.<ref>{{cite journal | vauthors = Muñoz-Huerta RF, Guevara-Gonzalez RG, Contreras-Medina LM, Torres-Pacheco I, Prado-Olivarez J, Ocampo-Velazquez RV | title = A review of methods for sensing the nitrogen status in plants: advantages, disadvantages and recent advances | journal = Sensors | volume = 13 | issue = 8 | pages = 10823–10843 | date = August 2013 | pmid = 23959242 | pmc = 3812630 | doi = 10.3390/s130810823 | doi-access = free | bibcode = 2013Senso..1310823M }}</ref><ref>{{cite journal | vauthors = Martin PD, Malley DF, Manning G, Fuller L |title=Determination of soil organic carbon and nitrogen at the field level using near-infrared spectroscopy |journal=Canadian Journal of Soil Science |date=November 2002 |volume=82 |issue=4 |pages=413–422 |doi=10.4141/S01-054 }}</ref>

==Digestion==

{{main|Proteolysis}}

[[File:Proteolysis scheme.svg|thumb|class=skin-invert-image|230px|Hydrolysis of protein.  X = HCl and heat for industrial proteolysis.  X = protease for biological proteolysis]]

In the absence of catalysts, proteins are slow to [[Hydrolysis|hydrolyze]].<ref name="Radzicka Wolfenden 1996">{{cite journal |last1=Radzicka |first1=Anna |last2=Wolfenden |first2=Richard |title=Rates of Uncatalyzed Peptide Bond Hydrolysis in Neutral Solution and the Transition State Affinities of Proteases |journal=Journal of the American Chemical Society |volume=118 |issue=26 |date=1 January 1996  |doi=10.1021/ja954077c |pages=6105–6109|bibcode=1996JAChS.118.6105R }}</ref> The breakdown of proteins to small peptides and amino acids ([[proteolysis]]) is a step in [[digestion]]; these breakdown products are then absorbed in the small intestine<!--[[jejunum]]-->.<ref name="Keller 2013">{{cite book |last=Keller |first=J. |title=Encyclopedia of Biological Chemistry |chapter=Gastrointestinal Digestion and Absorption |publisher=Elsevier |date=2013 |isbn=978-0-12-378631-9 |doi=10.1016/b978-0-12-378630-2.00106-7 |pages=354–359}}</ref> The hydrolysis of proteins relies on enzymes called [[protease]]s or peptidases.  Proteases, which are themselves proteins, come in several types according to the particular [[peptide bond]]s that they cleave as well as their tendency to cleave peptide bonds at the terminus of a protein (exopeptidases) vs peptide bonds at the interior of the protein (endopeptidases).<ref>{{cite journal |last=Oda |first=Kohei |title=New families of carboxyl peptidases: serine-carboxyl peptidases and glutamic peptidases  |journal=Journal of Biochemistry |year= 2012 |volume=151 |issue=1 |pages=13–25 |doi= 10.1093/jb/mvr129 |pmid= 22016395 |doi-access=free}}</ref>  [[Pepsin]] is an endopeptidase in the stomach.  Subsequent to the stomach, the pancreas secretes other proteases to complete the hydrolysis, these include [[trypsin]] and [[chymotrypsin]].<ref name="Switzar Giera 2013">{{cite journal |last1=Switzar |first1=Linda |last2=Giera |first2=Martin |last3=Niessen |first3=Wilfried M. A. |title=Protein Digestion: An Overview of the Available Techniques and Recent Developments |journal=Journal of Proteome Research |volume=12 |issue=3 |date=1 March 2013 |doi=10.1021/pr301201x |pages=1067–1077|pmid=23368288 }}</ref>

Protein hydrolysis is employed commercially as a means of producing amino acids from bulk sources of protein, such as blood meal, feathers, keratin.  Such materials are treated with hot [[hydrochloric acid]], which effects the hydrolysis of the peptide bonds.<ref>{{cite book |doi=10.1002/14356007.a02_057.pub2 |chapter=Amino Acids |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2007 |last1=Drauz |first1=Karlheinz |last2=Grayson |first2=Ian |last3=Kleemann |first3=Axel |last4=Krimmer |first4=Hans-Peter |last5=Leuchtenberger |first5=Wolfgang |last6=Weckbecker |first6=Christoph |isbn=978-3-527-30385-4 }}</ref>

== Mechanical properties ==

The [[Mechanical properties of biomaterials|mechanical properties]] of proteins are highly diverse and are often central to their biological function, as in the case of proteins like [[keratin]] and [[collagen]].<ref>{{cite journal | vauthors = Gosline J, Lillie M, Carrington E, Guerette P, Ortlepp C, Savage K | title = Elastic proteins: biological roles and mechanical properties | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 357 | issue = 1418 | pages = 121–132 | date = February 2002 | pmid = 11911769 | pmc = 1692928 | doi = 10.1098/rstb.2001.1022 | veditors = Bailey AJ, Macmillan J, Shrewry PR, Tatham AS }}</ref> For instance, the ability of [[Muscle|muscle tissue]] to continually expand and contract is directly tied to the elastic properties of their underlying protein makeup.<ref>{{cite journal | vauthors = Maruyama K, Natori R, Nonomura Y | title = New elastic protein from muscle | journal = Nature | volume = 262 | issue = 5563 | pages = 58–60 | date = July 1976 | pmid = 934326 | doi = 10.1038/262058a0 | bibcode = 1976Natur.262...58M }}</ref><ref>{{cite journal | vauthors = Tskhovrebova L, Trinick J | title = Making muscle elastic: the structural basis of myomesin stretching | journal = PLOS Biology | volume = 10 | issue = 2 | pages = e1001264 | date = February 2012 | pmid = 22347814 | pmc = 3279349 | doi = 10.1371/journal.pbio.1001264 | doi-access = free }}</ref> Beyond fibrous proteins, the conformational dynamics of [[enzyme]]s<ref>{{cite journal | vauthors = Mizraji E, Acerenza L, Lin J | title = Viscoelastic models for enzymes with multiple conformational states | journal = Journal of Theoretical Biology | volume = 129 | issue = 2 | pages = 163–175 | date = November 1987 | pmid = 3455460 | doi = 10.1016/s0022-5193(87)80010-3 | bibcode = 1987JThBi.129..163M }}</ref>  and the structure of [[biological membrane]]s, among other biological functions, are governed by the mechanical properties of the proteins. Outside of their biological context, the unique mechanical properties of many proteins, along with their relative sustainability when compared to [[List of synthetic polymers|synthetic polymers]], have made them desirable targets for next-generation materials design.<ref>{{Cite journal | vauthors = Schiller T, Scheibel T |date=2024-04-18 |title=Bioinspired and biomimetic protein-based fibers and their applications |journal=Communications Materials |volume=5 |issue=1 |page=56 |doi=10.1038/s43246-024-00488-2 |doi-access=free |bibcode=2024CoMat...5...56S }}</ref><ref>{{cite journal | vauthors = Sun J, He H, Zhao K, Cheng W, Li Y, Zhang P, Wan S, Liu Y, Wang M, Li M, Wei Z, Li B, Zhang Y, Li C, Sun Y, Shen J, Li J, Wang F, Ma C, Tian Y, Su J, Chen D, Fan C, Zhang H, Liu K | title = Protein fibers with self-recoverable mechanical properties via dynamic imine chemistry | journal = Nature Communications | volume = 14 | issue = 1 | pages = 5348 | date = September 2023 | pmid = 37660126 | pmc = 10475138 | doi = 10.1038/s41467-023-41084-1 | bibcode = 2023NatCo..14.5348S }}</ref>

[[Young's modulus]], ''E,''  is calculated as the axial stress σ over the resulting strain ε. It is a measure of the relative [[stiffness]] of a material. In the context of proteins, this stiffness often directly correlates to biological function. For example, [[collagen]], found in [[connective tissue]], [[bone]]s, and [[cartilage]], and [[keratin]], found in nails, claws, and hair, have observed stiffnesses that are several orders of magnitude higher than that of [[elastin]],<ref name="Guthold-2007">{{cite journal | vauthors = Guthold M, Liu W, Sparks EA, Jawerth LM, Peng L, Falvo M, Superfine R, Hantgan RR, Lord ST | title = A comparison of the mechanical and structural properties of fibrin fibers with other protein fibers | journal = Cell Biochemistry and Biophysics | volume = 49 | issue = 3 | pages = 165–181 | date = 2007-10-02 | pmid = 17952642 | pmc = 3010386 | doi = 10.1007/s12013-007-9001-4 }}</ref> which is though to give elasticity to structures such as [[blood vessel]]s, [[Lung|pulmonary tissue]], and [[Bladder|bladder tissue]], among others.<ref>{{cite journal | vauthors = Wang K, Meng X, Guo Z | title = Elastin Structure, Synthesis, Regulatory Mechanism and Relationship With Cardiovascular Diseases | journal = Frontiers in Cell and Developmental Biology | volume = 9 | pages = 596702 | date = 2021 | pmid = 34917605 | pmc = 8670233 | doi = 10.3389/fcell.2021.596702 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Debelle L, Tamburro AM | title = Elastin: molecular description and function | journal = The International Journal of Biochemistry & Cell Biology | volume = 31 | issue = 2 | pages = 261–272 | date = February 1999 | pmid = 10216959 | doi = 10.1016/S1357-2725(98)00098-3 }}</ref> In comparison to this, [[globular protein]]s, such as [[Bovine serum albumin|Bovine Serum Albumin]], which float relatively freely in the [[cytosol]] and often function as enzymes (and thus undergoing frequent conformational changes) have comparably much lower Young's moduli.<ref name="Khoury-2019">{{cite journal | vauthors = Khoury LR, Popa I | title = Chemical unfolding of protein domains induces shape change in programmed protein hydrogels | journal = Nature Communications | volume = 10 | issue = 1 | pages = 5439 | date = November 2019 | pmid = 31784506 | pmc = 6884551 | doi = 10.1038/s41467-019-13312-0 | bibcode = 2019NatCo..10.5439K }}</ref><ref>{{cite journal | vauthors = Tan R, Shin J, Heo J, Cole BD, Hong J, Jang Y | title = Tuning the Structural Integrity and Mechanical Properties of Globular Protein Vesicles by Blending Crosslinkable and NonCrosslinkable Building Blocks | journal = Biomacromolecules | volume = 21 | issue = 10 | pages = 4336–4344 | date = October 2020 | pmid = 32955862 | doi = 10.1021/acs.biomac.0c01147 }}</ref>

The Young's modulus of a single protein can be found through [[molecular dynamics]] simulation. Using either atomistic force-fields, such as [[CHARMM]] or [[GROMOS]], or coarse-grained forcefields like Martini,<ref>{{cite journal | vauthors = Souza PC, Alessandri R, Barnoud J, Thallmair S, Faustino I, Grünewald F, Patmanidis I, Abdizadeh H, Bruininks BM, Wassenaar TA, Kroon PC, Melcr J, Nieto V, Corradi V, Khan HM, Domański J, Javanainen M, Martinez-Seara H, Reuter N, Best RB, Vattulainen I, Monticelli L, Periole X, Tieleman DP, de Vries AH, Marrink SJ | title = Martini 3: a general purpose force field for coarse-grained molecular dynamics | journal = Nature Methods | volume = 18 | issue = 4 | pages = 382–388 | date = April 2021 | pmid = 33782607 | doi = 10.1038/s41592-021-01098-3 | url = https://pure.rug.nl/ws/files/190731140/s41592_021_01098_3.pdf }}</ref> a single protein molecule can be stretched by a uniaxial force while the resulting extension is recorded in order to calculate the strain.<ref>{{Cite web |title=Piotr Szymczak's Homepage |url=https://www.fuw.edu.pl/~piotrek/proteins.html |access-date=2024-05-13 |website=www.fuw.edu.pl}}</ref><ref>{{cite journal | vauthors = Mapplebeck S, Booth J, Shalashilin D | title = Simulation of protein pulling dynamics on second time scale with boxed molecular dynamics | journal = The Journal of Chemical Physics | volume = 155 | issue = 8 | pages = 085101 | date = August 2021 | pmid = 34470356 | doi = 10.1063/5.0059321 | bibcode = 2021JChPh.155h5101M | doi-access = free }}</ref> Experimentally, methods such as [[atomic force microscopy]] can be used to obtain similar data.<ref>{{cite journal | vauthors = Carrion-Vazquez M, Marszalek PE, Oberhauser AF, Fernandez JM | title = Atomic force microscopy captures length phenotypes in single proteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 20 | pages = 11288–11292 | date = September 1999 | pmid = 10500169 | pmc = 18026 | doi = 10.1073/pnas.96.20.11288 | doi-access = free | bibcode = 1999PNAS...9611288C }}</ref>

At the macroscopic level, the Young's modulus of cross-linked protein networks can be obtained through more traditional [[mechanical testing]]. Experimentally observed values for a few proteins can be seen below. 
{| class="wikitable"
|+Elasticity of Various Proteins
!Protein
!Protein Class
!Young's modulus
|-
|Keratin (Cross-Linked)
|Fibrous
|1.5-10 GPa<ref>{{Cite journal | vauthors = McKittrick J, Chen PY, Bodde SG, Yang W, Novitskaya EE, Meyers MA |date=2012-04-03 |title=The Structure, Functions, and Mechanical Properties of Keratin |url=http://link.springer.com/10.1007/s11837-012-0302-8 |journal=JOM |volume=64 |issue=4 |pages=449–468 |doi=10.1007/s11837-012-0302-8 |bibcode=2012JOM....64d.449M}}</ref>
|-
|Elastin (Cross-Linked)
|Fibrous
|1 MPa<ref name="Guthold-2007" />
|-
|Fibrin (Cross-linked)
|Fibrous
|1-10 MPa <ref name="Guthold-2007" />
|-
|Collagen (Cross-linked)
|Fibrous
|5-7.5 GPa<ref name="Guthold-2007" /><ref>{{cite journal | vauthors = Yang L, van der Werf KO, Fitié CF, Bennink ML, Dijkstra PJ, Feijen J | title = Mechanical properties of native and cross-linked type I collagen fibrils | journal = Biophysical Journal | volume = 94 | issue = 6 | pages = 2204–2211 | date = March 2008 | pmid = 18032556 | pmc = 2257912 | doi = 10.1529/biophysj.107.111013 | bibcode = 2008BpJ....94.2204Y }}</ref>
|-
|Resilin (Cross-Linked)
|Fibrous
|1-2 MPa<ref name="Guthold-2007" />
|-
|Bovine Serum Albumin (Cross-Linked)
|Globular 
|2.5-15 KPa<ref name="Khoury-2019" />
|-
|β-Barrel Outer Membrane Proteins
|Membrane
|20-45 GPa<ref>{{cite journal | vauthors = Lessen HJ, Fleming PJ, Fleming KG, Sodt AJ | title = Building Blocks of the Outer Membrane: Calculating a General Elastic Energy Model for β-Barrel Membrane Proteins | journal = Journal of Chemical Theory and Computation | volume = 14 | issue = 8 | pages = 4487–4497 | date = August 2018 | pmid = 29979594 | pmc = 6191857 | doi = 10.1021/acs.jctc.8b00377 }}</ref>
|}
<!--
=== Viscosity ===
In addition to serving as enzymes within the cell, [[globular protein]]s often act as key transport molecules. For instance, [[Serum albumin|Serum Albumins]], a key component of [[blood]], are necessary for the transport of a multitude of small molecules throughout the body.<ref>{{cite journal | vauthors = Mishra V, Heath RJ | title = Structural and Biochemical Features of Human Serum Albumin Essential for Eukaryotic Cell Culture | journal = International Journal of Molecular Sciences | volume = 22 | issue = 16 | pages = 8411 | date = August 2021 | pmid = 34445120 | pmc = 8395139 | doi = 10.3390/ijms22168411 | doi-access = free }}</ref> Because of this, the concentration dependent behavior of these proteins in solution is directly tied to the function of the [[circulatory system]]. One way of quantifying this behavior is through the [[viscosity]] of the solution.{{Citation needed|date=December 2024}}

Viscosity, η, is generally given is a measure of a fluid's resistance to deformation. It can be calculated as the ratio between the applied stress and the rate of change of the resulting shear strain, that is, the rate of deformation. Viscosity of complex liquid mixtures, such as blood, often depends strongly on temperature and solute concentration.<ref name="Spencer_2024">{{cite journal | vauthors = Spencer SJ, Ranganathan VT, Yethiraj A, Andrews GT | title = Concentration Dependence of Elastic and Viscoelastic Properties of Aqueous Solutions of Ficoll and Bovine Serum Albumin by Brillouin Light Scattering Spectroscopy | journal = Langmuir: The ACS Journal of Surfaces and Colloids | volume = 40 | issue = 9 | pages = 4615–4622 | date = March 2024 | pmid = 38387073 | doi = 10.1021/acs.langmuir.3c02967 | arxiv = 2309.10967 }}</ref> For serum albumin, specifically [[bovine serum albumin]], the following relation between viscosity and [[temperature]] and [[concentration]] can be used.<ref>{{cite journal | vauthors = Monkos K | title = Viscosity of bovine serum albumin aqueous solutions as a function of temperature and concentration | journal = International Journal of Biological Macromolecules | volume = 18 | issue = 1–2 | pages = 61–68 | date = February 1996 | pmid = 8852754 | doi = 10.1016/0141-8130(95)01057-2 }}</ref>

<math>\eta = \exp\left[ \frac{c}{\alpha-\beta\ c}\left(-B +D T + \frac{\Delta E}{R T}\right)\right] </math>

Where ''c'' is the concentration, ''T'' is the temperature, ''R'' is the [[gas constant]], and α, β, ''B'', ''D'', and Δ''E'' are all material-based property constants. This equation has the form of an [[Arrhenius equation]], assigning viscosity an exponential dependence on temperature and concentration.
-->

== See also ==

{{columns-list|colwidth=30em|
* [[Deproteination]]
* [[DNA-binding protein]]
* [[Macromolecule]]
* [[Index of protein-related articles]]
* [[Intein]]
* [[List of proteins]]
* [[Proteopathy]]
* [[Proteopedia]]
* [[Sequence space (evolution)|Protein sequence space]]
* [[Protein superfamily]]
* [[Molecular evolution|Protein evolution]]

}}{{Clear}}

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}}

==Further reading ==

; Textbooks
{{refbegin|32em}}
* {{cite book |vauthors=Branden C, Tooze J |title=Introduction to Protein Structure |publisher=Garland Pub |location=New York |year=1999 |isbn=978-0-8153-2305-1 |ref=none}}
* {{cite book |vauthors=Murray RF, Harper HW, Granner DK, Mayes PA, Rodwell VW |title=Harper's Illustrated Biochemistry |publisher=Lange Medical Books/McGraw-Hill |location=New York |year=2006 |isbn=978-0-07-146197-9 |ref=none}}
* {{cite book |vauthors=Van Holde KE, Mathews CK |title=Biochemistry |publisher=Benjamin/Cummings Pub. Co., Inc |location=Menlo Park, California |year=1996 |isbn=978-0-8053-3931-4 |url=https://archive.org/details/biochemistry00math |ref=none}}
{{refend}}

; History
* {{cite book | last1=Tanford | first1=Charles | last2=Reynolds | first2=Jacqueline Ann | title=Nature's Robots: A History of Proteins | publisher=Oxford University Press, USA | publication-place=Oxford New York | date=2001 | isbn=978-0-19-850466-5 |ref=none}}

== External links ==

{{Sister project links|auto=1|wikt=protein}}

===Databases and projects===

* [https://www.ncbi.nlm.nih.gov/sites/entrez?db=protein NCBI Entrez Protein database]
* [https://www.ncbi.nlm.nih.gov/sites/entrez?db=structure NCBI Protein Structure database]
* [https://web.archive.org/web/20060424071622/http://www.hprd.org/ Human Protein Reference Database]
* [https://web.archive.org/web/20070314135408/http://www.humanproteinpedia.org/ Human Proteinpedia]
* [http://folding.stanford.edu/ Folding@Home (Stanford University)] {{Webarchive|url=https://web.archive.org/web/20120908075542/http://folding.stanford.edu/English/HomePage |date=2012-09-08 }}
* [http://www.pdbe.org/ Protein Databank in Europe] (see also [https://archive.today/20130727184433/http://www.pdbe.org/quips PDBeQuips], short articles and tutorials on interesting PDB structures)
* [http://www.rcsb.org/ Research Collaboratory for Structural Bioinformatics] (see also [http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] {{Webarchive|url=https://web.archive.org/web/20200724151351/https://www.rcsb.org/pdb/static.do?p=education_discussion%2Fmolecule_of_the_month%2Findex.html |date=2020-07-24 }}, presenting short accounts on selected proteins from the PDB)
* [http://www.proteopedia.org/ Proteopedia – Life in 3D]: rotatable, zoomable 3D model with wiki annotations for every known protein molecular structure.
* [https://web.archive.org/web/20080608183902/http://www.expasy.uniprot.org/ UniProt the Universal Protein Resource]

===Tutorials and educational websites===

* [https://web.stanford.edu/group/hopes/cgi-bin/hopes_test/an-introduction-to-proteins/ "An Introduction to Proteins"] from [[HOPES]] (Huntington's Disease Outreach Project for Education at Stanford)
* [https://web.archive.org/web/20050219090405/http://www.biochemweb.org/proteins.shtml Proteins: Biogenesis to Degradation – The Virtual Library of Biochemistry and Cell Biology]

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