Post-translational modification (PTM) refers to the covalent and generally enzymatic modification of proteins following protein biosynthesis. It can impact the structure, electrophilicity and interactions of proteins. These modifications regulate protein folding by targeting specific subcellular compartments, interacting with ligands or other proteins, or by bringing about a change in their functional state including catalytic activity or signaling.
PTMs can happen at any step of the protein lifespan. Many proteins are modified shortly after translation is completed to mediate proper folding or to direct the nascent protein to distinct cellular locations (such as the nucleus or membrane). Other modifications occur after folding and localization are completed to activate or inactivate catalytic activity. Proteins are also covalently linked to tags that target a protein for degradation. They are modified through a combination of post-translational cleavage and the addition of functional groups through a stepwise mechanism of protein maturation or activation.
PTMs occur at distinct amino acid side chains or peptide linkages and are most often mediated by enzymatic activity. Many proteins can also modify themselves using autocatalytic domains, such as autokinase and autoproteolytic domains. PTMs can also be reversible based on the nature of the modification.
Post translational modifications play an important part in modifying the end product of expression and contribute towards biological processes and diseased conditions. The amino terminal sequences are removed by proteolytic cleavage when the proteins cross the membranes. These amino terminal sequences target the proteins for transporting them to their actual point of action in the cell.
Protein post translational modifications may happen in many ways. Some of them are listed below:
- Glycosylation: Glycosylation in proteins results in addition of a glycosyl group to either asparagine, hydroxylysine, serine, or threonine. Software for studying glycosylation by glycan structure prediction.
- Acetylation: The addition of an acetyl group, usually at the N-terminus of the protein.
- 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.)
- Biotinylation: Acylation of conserved lysine residues with a biotin appendage.
- Glutamylation: Covalent linkage of glutamic acid residues to tubulin and some other proteins.
- Glycylation: Covalent linkage of one to more than 40 glycine residues to the tubulin C-terminal tail of the amino acid sequence.
- Isoprenylation: The addition of an isoprenoid group (e.g. farnesol and geranylgeraniol).
- Lipoylation: The attachment of a lipoate functionality.
- 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.
- Sulfation: The addition of a sulfate group to a tyrosine.
- Ubiquitination: Ubiquitination involves addition of a protein found ubiquitously, termed ‘ubiquitin’, to the lysine residue of a substrate. Either a single ubiquitin molecule (monoubiquitination) or a chain of several ubiquitin molecules may be attached (polyubiquitination).
- Lipidation: The covalent binding of a lipid group to a protein is called lipidation. Lipidation can be further subdivided into prenylation, N-myristoylation, palmitoylation, and glycosylphosphatidylinositol (GPI)-anchor addition.
- AMPylation: AMPylation refers to reversible addition of AMP to a protein. It involves formation of a phosphodiester bond between the hydroxyl group of the protein and the phosphate group of AMP.
- C-terminal amidation
Tools used for PTMs prediction
- Tandem mass spectrometry
- Proximity Ligation Assay
- Immunofluorescence for global PTM
- Mass spectrometry after IP enrichment
- western blot analysis
Databases of PTMs
- Human Protein Reference Database
- Protein Information Resource (PIR)