Post-translational modifications (PTMs) are covalent chemical changes that occur to proteins after they have been synthesized by the ribosome. PTMs greatly expand the functional diversity of the proteome by altering protein activity, localization, stability, and interactions.
Common Types of Post-Translational Modifications
Phosphorylation
Phosphorylation is the addition of a phosphate group to serine, threonine, or tyrosine residues by protein kinases. It is one of the most common and important PTMs, acting as a molecular switch that regulates enzyme activity, signal transduction, and protein-protein interactions. Phosphatases remove phosphate groups, providing reversibility.
Glycosylation
Glycosylation is the attachment of carbohydrate chains to proteins. In N-linked glycosylation, sugars are attached to asparagine residues. In O-linked glycosylation, they are attached to serine or threonine. Glycosylation affects protein folding, stability, and cell-cell recognition. It is especially important for membrane and secreted proteins.
Ubiquitination
Ubiquitination is the attachment of ubiquitin — a small regulatory protein — to lysine residues. A chain of four or more ubiquitin molecules targets the protein for degradation by the proteasome. Monoubiquitination can alter protein localization and activity. This modification is central to protein turnover and quality control.
Acetylation
Acetylation is the addition of an acetyl group to lysine residues (on histones) or to the N-terminus of proteins. Histone acetylation relaxes chromatin structure, promoting gene expression. N-terminal acetylation affects protein stability and targeting.
Methylation
Methylation is the addition of methyl groups to lysine and arginine residues, most commonly on histones. Depending on the specific residue and degree of methylation, it can activate or repress gene expression. Arginine methylation is also involved in RNA processing and signal transduction.
Disulfide Bond Formation
Disulfide bonds form between cysteine residues in oxidizing environments such as the endoplasmic reticulum. These covalent cross-links stabilize protein tertiary and quaternary structure, particularly in secreted and extracellular proteins.
Other Modifications
Many other PTMs exist, including lipidation (attachment of lipid groups for membrane anchoring), SUMOylation (similar to ubiquitination but regulates function rather than degradation), nitrosylation, and hydroxylation. Mass spectrometry is the primary tool for identifying and characterizing PTMs.
