Editing Post-translational modification (section)

{{short description|Chemical changes in proteins following their translation from mRNA}}
[[File:Insulin path.svg|right|thumb|upright=1.35|Post-translational modification of [[insulin]]. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the [[endoplasmic reticulum]], where it is cut, folded, and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the [[golgi apparatus]], where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.]]

In [[molecular biology]], '''post-translational modification''' ('''PTM''') is the [[covalent]] process of changing [[protein]]s following [[protein biosynthesis]]. PTMs may involve [[enzymes]] or occur spontaneously. Proteins are created by [[ribosomes]], which [[translation (biology)|translate]] [[mRNA]] into [[polypeptide chain]]s, which may then change to form the mature protein product. PTMs are important components in cell [[signal transduction|signalling]], as for example when [[prohormone]]s are converted to [[hormone]]s.

Post-translational modifications can occur on the [[amino acid]] [[side chain]]s or at the protein's [[C-terminus|C-]] or [[N-terminus|N-]] termini.<ref>{{cite book|last1=Pratt|first1=Charlotte W.|authorlink1=Charlotte W. Pratt|authorlink2=Judith G. Voet|authorlink3=Donald Voet|first2=Judith G.|last2=Voet|last3=Voet|first3=Donald|url=https://books.google.com/books?id=h0FCAQAAIAAJ|title=Fundamentals of Biochemistry: Life at the Molecular Level|date=2006|publisher=Wiley|location=Hoboken, NJ|oclc=1280801548|isbn=9780471214953|archive-date=13 July 2012|archive-url=https://archive.org/details/fundamentalsofbi00voet_0|edition=2nd }}</ref> They can expand the chemical set of the 22 [[proteinogenic amino acid|amino acids]] by changing an existing [[functional group]] or adding a new one such as phosphate. [[Phosphorylation]] is highly effective for controlling the enzyme activity and is the most common change after translation. <ref name="khoury">{{cite journal|vauthors=Khoury GA, Baliban RC, Floudas CA|author-link3=Christodoulos Floudas|date=September 2011|title=Proteome-wide post-translational modification statistics: frequency analysis and curation of the swiss-prot database|journal=[[Scientific Reports]]|volume=1|pages=90|bibcode=2011NatSR...1...90K|doi=10.1038/srep00090|pmc=3201773|pmid=22034591}}</ref> Many [[eukaryotic]] and [[prokaryotic]] proteins also have [[carbohydrate]] molecules attached to them in a process called [[glycosylation]], which can promote [[protein folding]] and improve stability as well as serving regulatory functions. Attachment of [[lipid]] molecules, known as [[lipidation]], often targets a protein or part of a protein attached to the [[cell membrane]].

Other forms of post-translational modification consist of cleaving [[peptide bond]]s, as in processing a [[propeptide]] to a mature form or removing the initiator [[methionine]] residue. The formation of [[disulfide bond]]s from [[cysteine]] residues may also be referred to as a post-translational modification.<ref name=lodish>{{cite book|vauthors=Lodish H, Berk A, Zipursky SL|display-authors=etal|chapter=17.6, Post-Translational Modifications and Quality Control in the Rough ER|title=Molecular Cell Biology|date=2000|publisher=W. H. Freeman|location=New York|isbn=978-0-7167-3136-8|edition=4th|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK21741/|url=https://archive.org/details/molecularcellbio00lodi}}</ref> For instance, the peptide [[hormone]] [[insulin]] is cut twice after disulfide bonds are formed, and a [[propeptide]] is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds.

Some types of post-translational modification are consequences of [[oxidative stress]]. [[Carbonylation]] is one example that targets the modified protein for degradation and can result in the formation of protein aggregates.<ref>{{cite journal|vauthors=Dalle-Donne I, Aldini G, Carini M, Colombo R, Rossi R, Milzani A|year=2006|title=Protein carbonylation, cellular dysfunction, and disease progression|journal=[[Journal of Cellular and Molecular Medicine]]|volume=10|issue=2|pages=389–406|doi=10.1111/j.1582-4934.2006.tb00407.x|pmc=3933129|pmid=16796807}}</ref><ref>{{cite journal|vauthors=Grimsrud PA, Xie H, Griffin TJ, Bernlohr DA|date=August 2008|title=Oxidative stress and covalent modification of protein with bioactive aldehydes|journal=[[The Journal of Biological Chemistry]]|volume=283|issue=32|pages=21837–41|doi=10.1074/jbc.R700019200|pmc=2494933|pmid=18445586|doi-access=free}}</ref> Specific amino acid modifications can be used as [[biomarker]]s indicating oxidative damage.<ref>{{cite journal | vauthors = Gianazza E, Crawford J, Miller I | title = Detecting oxidative post-translational modifications in proteins | journal = Amino Acids | volume = 33 | issue = 1 | pages = 51–6 | date = July 2007 | pmid = 17021655 | doi = 10.1007/s00726-006-0410-2 | s2cid = 23819101 }}</ref>
PTMs and metal ions play a crucial and reciprocal role in regulating protein function, influencing cellular processes such as signal transduction and gene expression, with dysregulated interactions implicated in diseases like cancer and neurodegenerative disorders.<ref>{{cite journal |last1=Peana |first1=Massimiliano |title=Interplay of Metal Ions and Posttranslational Modifications in Proteins |journal=European Journal of Inorganic Chemistry |date=19 August 2024 |volume=27 |issue=27 |doi=10.1002/ejic.202400175 |url=https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/ejic.202400175|url-access=subscription }}</ref>

Sites that often undergo post-translational modification are those that have a functional group that can serve as a [[nucleophile]] in the reaction: the [[hydroxyl]] groups of [[serine]], [[threonine]], and [[tyrosine]]; the [[amine]] forms of [[lysine]], [[arginine]], and [[histidine]]; the [[thiolate]] [[anion]] of [[cysteine]]; the [[carboxylate]]s of [[aspartate]] and [[glutamate]]; and the N- and C-termini. In addition, although the [[amide]] of [[asparagine]] is a weak nucleophile, it can serve as an attachment point for [[glycan]]s. Rarer modifications can occur at oxidized [[methionine]]s and at some [[methylene group]]s in side chains.<ref name=walsh>{{cite book|last1=Walsh|first1=Christopher T.|title=Posttranslational modification of proteins : expanding nature's inventory|date=2006|publisher=Roberts and Co. Publ.|location=Englewood|isbn=9780974707730}} {{rp|12–14}}</ref>

Post-translational modification of proteins can be experimentally detected by a variety of techniques, including [[mass spectrometry]], [[Eastern blotting]], and [[Western blotting]].