myristoylation

Myristoylation is a lipid modification in which a myristoyl group, a 14-carbon saturated fatty acid, is covalently attached to a protein, most commonly to the amino-terminal glycine residue via an amide bond. This modification is usually co-translational, occurring as the nascent polypeptide emerges from the ribosome.

The enzymatic step is catalyzed by N-myristoyltransferases (NMTs), which use myristoyl-CoA as the donor substrate. In most cases the initiator methionine is removed by methionine aminopeptidase, exposing glycine at position 2, which is then recognized by NMT and myristoylated. In humans, two isoforms, NMT1 and NMT2, mediate the reaction, with similar enzymes found across eukaryotes.

Biological consequences of myristoylation include increased hydrophobicity and membrane association, altered subcellular localization, and effects on protein–protein interactions and stability. The modification is often essential for the function of signaling proteins such as certain G proteins and Src-family kinases. It is generally irreversible, though additional trafficking and regulatory steps can modulate protein activity.

There are also post-translational contexts in which myristoylation occurs after proteolytic processing to reveal a new N-terminus with glycine, and in rare cases myristoylation may occur on internal glycine residues. Myristoylation often works in concert with other lipid modifications, such as palmitoylation, to strengthen membrane binding.

Clinically and biologically, NMTs are conserved and essential in many organisms; inhibitors of NMT are explored as potential therapeutics for cancer and parasitic diseases. Detection and study commonly employ metabolic labeling and proteomic approaches.