2.4 The covalent modification of proteins
Many proteins are modified by the covalent linking of groups that can affect their function and/or localisation in the cell. Such covalent modifications occur after synthesis and folding of the polypeptide component. The main types of covalent modification and their functions are listed below.
Methylation/acetylation of amino acids at the N-terminal tails of histone proteins in eukaryotes can affect the structure of chromatin and ultimately gene expression. Prokaryotes also use methylation as a means of directly regulating protein activities. For example, the methylation of specific proteins controlling flagellar movement is an important mechanism for the regulation of bacterial chemotaxis.
Phosphorylation of proteins (catalysed by specific kinases) is a key regulatory mechanism in eukaryotic intracellular signalling and in metabolic pathways.
Lipidation of proteins (i.e. addition of lipid tails) targets them to cell membranes (plasma membrane and cell organelles).
Glycosylation is a feature of many extracellular proteins, whether secreted or on the cell surface, and may offer the protein some protection against proteases.
These modifications are catalysed by specific enzymes and can be reversed, permitting regulation of the protein's function. This reversibility is particularly significant with respect to protein phosphorylation (discussed further in Section 5.3).