Posttranslational modification (PTM) is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis for many proteins.

The bottom of this diagram shows the modification of primary structure of insulin, as described.

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated in proteins. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching to it other biochemical functional groups such as acetate, phosphate, various lipids and carbohydrates, by changing the chemical nature of an amino acid (e.g. citrullination) or by making structural changes, like the formation of disulfide bridges.

Also, enzymes may remove amino acids from the amino end of the protein, or cut the peptide chain in the middle. 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.

Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

PTMs involving addition of functional groups

The genetic code diagram^[1] showing the amino acid residues as target of modification.

PTMs involving addition include:

• acylation
  • acetylation, the addition of an acetyl group, either at the N-terminus^[2] of the protein or at lysine residues ^[3]

(also see histone acetylation)^[4][5]

• • deacetylation
• alkylation, the addition of an alkyl group (e.g. methyl, ethyl)
  • methylation the addition of a methyl group, usually at lysine or arginine residues. (This is a type of alkylation.)
  • demethylation
• amidation at C-terminus
• biotinylation, acylation of conserved lysine residues with a biotin appendage
• formylation
• gamma-carboxylation dependent on Vitamin K^[6]
• glutamylation, covalent linkage of glutamic acid residues to tubulin and some other proteins.^[7] (See tubulin polyglutamylase)
• glycosylation, the addition of a glycosyl group to either asparagine, hydroxylysine, serine, or threonine, resulting in a glycoprotein. Distinct from glycation, which is regarded as a nonenzymatic attachment of sugars.
• glycylation, covalent linkage of one to more than 40 glycine residues to the tubulin C-terminal tail
• heme moiety may be covalently attached
• hydroxylation
• iodination (e.g. of thyroid hormones)
• isoprenylation, the addition of an isoprenoid group (e.g. farnesol and geranylgeraniol)
• lipoylation, attachment of a lipoate functionality
  • prenylation
  • GPI anchor formation
    • myristoylation
    • farnesylation
    • geranylgeranylation
• nucleotides or derivatives thereof may be covalently attached
  • ADP-ribosylation
  • flavin attachment
• oxidation
• palmitoylation
• pegylation
• phosphatidylinositol may be covalently attached
• phosphopantetheinylation, the addition of a 4'-phosphopantetheinyl moiety from coenzyme A, as in fatty acid, polyketide, non-ribosomal peptide and leucine biosynthesis
• phosphorylation, the addition of a phosphate group, usually to serine, tyrosine, threonine or histidine
• polysialylation, addition of polysialic acid, PSA to NCAM
• pyroglutamate formation
• racemization of proline by prolyl isomerase
• tRNA-mediation addition of amino acids such as arginylation
• sulfation, the addition of a sulfate group to a tyrosine.
• selenoylation (co-translational incorporation of selenium in selenoproteins)
• sulfation

PTMs involving addition of other proteins or peptides

• ISGylation, the covalent linkage to the ISG15 protein (Interferon-Stimulated Gene 15)^[8]
• SUMOylation, the covalent linkage to the SUMO protein (Small Ubiquitin-related MOdifier)^[9]
• ubiquitination, the covalent linkage to the protein ubiquitin.

PTMs involving changing the chemical nature of amino acids

• citrullination, or deimination the conversion of arginine to citrulline
• deamidation, the conversion of glutamine to glutamic acid or asparagine to aspartic acid

PTMs involving structural changes

• disulfide bridges, the covalent linkage of two cysteine amino acids
• proteolytic cleavage, cleavage of a protein at a peptide bond

Case examples

• cleavage and formation of disulfide bridges during the production of insulin
• PTM of histones as regulation of transcription: RNA polymerase control by chromatin structure
• PTM of RNA polymerase II as regulation of transcription: RNA polymerase II

External links

• deltaMasses: Differential PTM Detection after mass spectrometry
• AutoMotif Server: A Computational Protocol for Identification of Post-Translational Modifications in Protein Sequences
• Functional analyses for site-specific phosphorylation of a target protein in cells

References

1. ^ Gramatikoff K. in Abgent Catalog (2004-5) p.263
2. ^ Polevoda B, Sherman F (2003). "N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins". J Mol Biol 325 (4): 595-622. PMID 12507466. 
3. ^ Yang XJ, Seto E (2008). "Lysine acetylation: codified crosstalk with other posttranslational modifications". Mol Cell 31: 449-61. PMID 18722172. 
4. ^ Bártová E, Krejcí J, Harnicarová A, Galiová G, Kozubek S (2008). "Histone modifications and nuclear architecture: a review". J Histochem Cytochem 56 (8): 711-21. PMID 18474937. 
5. ^ Glozak MA, Sengupta N, Zhang X, Seto E (2005). "Acetylation and deacetylation of non-histone proteins". Gene 363: 15-23. PMID 16289629. 
6. ^ Walker CS, Shetty RP, Clark K, et al (2001). "On a potential global role for vitamin K-dependent gamma-carboxylation in animal systems. Evidence for a gamma-glutamyl carboxylase in Drosophila". J. Biol. Chem. 276 (11): 7769–74. doi:10.1074/jbc.M009576200. PMID 11110799. 
7. ^ Eddé B, Rossier J, Le Caer JP, Desbruyères E, Gros F, Denoulet P (1990). "Posttranslational glutamylation of alpha-tubulin". Science 247 (4938): 83–5. doi:10.1126/science.1967194. PMID 1967194. 
8. ^ Malakhova, Oxana A.; Yan, Ming; Malakhov, Michael P.; Yuan, Youzhong; Ritchie, Kenneth J.; Kim, Keun Il; Peterson, Luke F.; Shuai, Ke; and Dong-Er Zhang (2003). "Protein ISGylation modulates the JAK-STAT signaling pathway". Genes & Development 17 (4): 455–60. doi:10.1101/gad.1056303. PMID 12600939. 
9. ^ Van G. Wilson (Ed.) (2004). Sumoylation: Molecular Biology and Biochemistry. Horizon Bioscience. ISBN 0-9545232-8-8.