Editing Protein structure (section)

==Levels of protein structure==
There are four distinct levels of protein structure.
[[File:Protein structure.png|thumb|upright=1.8|Four levels of protein structure]]

===Primary structure===
{{Main|Protein primary structure}}
The [[primary structure]] of a protein refers to the sequence of [[amino acid]]s in the polypeptide chain. The primary structure is held together by [[peptide bonds]] that are made during the process of [[protein biosynthesis]]. The two ends of the [[polypeptide chain]] are referred to as the [[carboxyl terminus]] (C-terminus) and the [[amino terminus]] (N-terminus) based on the nature of the free group on each extremity. Counting of residues always starts at the N-terminal end (NH<sub>2</sub>-group), which is the end where the amino group is not involved in a peptide bond. The primary structure of a protein is determined by the [[gene]] corresponding to the protein. A specific sequence of [[nucleotide]]s in [[DNA]] is [[transcription (genetics)|transcribed]] into [[mRNA]], which is read by the [[ribosome]] in a process called [[translation (biology)|translation]]. The sequence of amino acids in insulin was discovered by [[Frederick Sanger]], establishing that proteins have defining amino acid sequences.<ref>{{cite journal | vauthors = Sanger F, Tuppy H | title = The amino-acid sequence in the phenylalanyl chain of insulin. I. The identification of lower peptides from partial hydrolysates | journal = The Biochemical Journal | volume = 49 | issue = 4 | pages = 463–481 | date = September 1951 | pmid = 14886310 | pmc = 1197535 | doi = 10.1042/bj0490463 }}</ref><ref>{{cite journal | vauthors = Sanger F | title = Chemistry of insulin; determination of the structure of insulin opens the way to greater understanding of life processes | journal = Science | volume = 129 | issue = 3359 | pages = 1340–1344 | date = May 1959 | pmid = 13658959 | doi = 10.1126/science.129.3359.1340 | bibcode = 1959Sci...129.1340G }}</ref> The sequence of a protein is unique to that protein, and defines the structure and function of the protein. The sequence of a protein can be determined by methods such as [[Edman degradation]] or [[Mass spectrometry#Protein identification|tandem mass spectrometry]]. Often, however, it is read directly from the sequence of the gene using the [[genetic code]]. It is strictly recommended to use the words "amino acid residues" when discussing proteins because when a peptide bond is formed, a [[water molecule]] is lost, and therefore proteins are made up of amino acid residues. [[Post-translational modification]]s such as [[phosphorylation]]s and [[glycosylation]]s are usually also considered a part of the primary structure, and cannot be read from the gene. For example, [[insulin]] is composed of 51 amino acids in 2 chains. One chain has 31 amino acids, and the other has 20 amino acids.

===Secondary structure===
[[File:Alpha helix.png|thumb|100px|An α-helix with hydrogen bonds (yellow dots)]]
{{Main|Protein secondary structure}}
[[Secondary structure]] refers to highly regular local sub-structures on the actual polypeptide backbone chain. Two main types of secondary structure, the [[alpha helix|α-helix]] and the [[beta strand|β-strand]] or [[beta sheet|β-sheet]]s, were suggested in 1951 by [[Linus Pauling]].<ref name="Pauling1951">{{cite journal | vauthors = Pauling L, Corey RB, Branson HR | title = The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 37 | issue = 4 | pages = 205–211 | date = April 1951 | pmid = 14816373 | pmc = 1063337 | doi = 10.1073/pnas.37.4.205 | doi-access = free | bibcode = 1951PNAS...37..205P }}</ref> These secondary structures are defined by patterns of [[hydrogen bonds]] between the main-chain peptide groups. They have a regular geometry, being constrained to specific values of the dihedral angles ψ and φ on the [[Ramachandran plot]]. Both the α-helix and the β-sheet represent a way of saturating all the hydrogen bond donors and acceptors in the peptide backbone. Some parts of the protein are ordered but do not form any regular structures. They should not be confused with [[random coil]], an unfolded polypeptide chain lacking any fixed three-dimensional structure. Several sequential secondary structures may form a "[[supersecondary structure|supersecondary unit]]".<ref name="ChiangYS2007">{{cite journal | vauthors = Chiang YS, Gelfand TI, Kister AE, Gelfand IM | title = New classification of supersecondary structures of sandwich-like proteins uncovers strict patterns of strand assemblage | journal = Proteins | volume = 68 | issue = 4 | pages = 915–921 | date = September 2007 | pmid = 17557333 | doi = 10.1002/prot.21473 | s2cid = 29904865 }}</ref>

===Tertiary structure===
{{Main|Protein tertiary structure}}
[[Tertiary structure]] refers to the three-dimensional structure created by a single protein molecule (a single [[polypeptide chain]]). It may include [[Protein domain|one or several domains]]. The α-helices and β-pleated-sheets are folded into a compact [[globular structure]]. The folding is driven by the ''non-specific'' [[hydrophobic interactions]], the burial of [[hydrophobic residues]] from [[water]], but the structure is stable only when the parts of a [[protein domain]] are locked into place by ''specific'' tertiary interactions, such as [[salt bridge (protein and supramolecular)|salt bridges]], hydrogen bonds, and the tight packing of side chains and [[disulfide bond]]s. The disulfide bonds are extremely rare in cytosolic proteins, since the [[cytosol]] (intracellular fluid) is generally a [[redox|reducing]] environment.

===Quaternary structure===
{{Main|Protein quaternary structure}}
Quaternary structure is the three-dimensional structure consisting of the aggregation of two or more individual polypeptide chains (subunits) that operate as a single functional unit ([[multimer]]). The resulting multimer is stabilized by the same [[non-covalent interaction]]s and disulfide bonds as in tertiary structure. There are many possible quaternary structure organisations.<ref name="pmid19059267">{{cite journal | vauthors = Moutevelis E, Woolfson DN | title = A periodic table of coiled-coil protein structures | journal = Journal of Molecular Biology | volume = 385 | issue = 3 | pages = 726–732 | date = January 2009 | pmid = 19059267 | doi = 10.1016/j.jmb.2008.11.028 }}</ref> Complexes of two or more polypeptides (i.e. multiple subunits) are called [[multimer]]s. Specifically it would be called a [[dimer (chemistry)|dimer]] if it contains two subunits, a [[trimer (chemistry)|trimer]] if it contains three subunits, a [[tetramer]] if it contains four subunits, and a [[pentamer]] if it contains five subunits, and so forth. The subunits are frequently related to one another by [[symmetry group|symmetry operations]], such as a 2-fold axis in a dimer. Multimers made up of identical subunits are referred to with a prefix of "homo-" and those made up of different subunits are referred to with a prefix of "hetero-", for example, a heterotetramer, such as the two alpha and two beta chains of [[hemoglobin]].

===Homomers===

An assemblage of multiple copies of a particular [[polypeptide]] chain can be described as a [[homomeric|homomer]], [[multimer]] or [[oligomer]].  Bertolini et al. in 2021<ref name = Bertolini2021>{{cite journal |vauthors=Bertolini M, Fenzl K, Kats I, Wruck F, Tippmann F, Schmitt J, Auburger JJ, Tans S, Bukau B, Kramer G |title=Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly |journal=Science |volume=371 |issue=6524 |pages=57–64 |date=January 2021 |pmid=33384371 |pmc=7613021 |doi=10.1126/science.abc7151 |bibcode=2021Sci...371...57B |url=}}</ref> presented evidence that homomer formation may be driven by interaction between nascent polypeptide chains as they are translated from [[messenger RNA|mRNA]] by nearby adjacent [[ribosome]]s.  Hundreds of proteins have been identified as being assembled into homomers in human cells.<ref name = Bertolini2021/>  The process of assembly is often initiated by the interaction of the N-terminal region of polypeptide chains. Evidence that numerous gene products form homomers (multimers) in a variety of organisms based on [[complementation (genetics)|intragenic complementation]] evidence was reviewed in 1965.<ref>{{cite journal |vauthors=BERNSTEIN H, EDGAR RS, DENHARDT GH |title=Intragenic Complementation Among Temperature Sensitive Mutants of Bacteriophage T4D |journal=Genetics |volume=51 |issue=6 |pages=987–1002 |date=June 1965 |pmid=14337770 |pmc=1210828 |doi=10.1093/genetics/51.6.987 |url=}}</ref>