Membrane Targeting via Protein N-Myristoylation

The covalent modification of cell proteins by the attachment of myristic acid, a 14 carbon saturated fatty acid, to their N-terminal amino acid is now recognized to be a widespread phenomenon (1–5). The enzyme responsible for the attachment of myristic acid to these proteins is myristoyl-CoA: Protein N-myristoyltransferase (NMT; EC 2.3.1.97). This enzyme catalyzes the transfer of myristic acid from myristoyl-CoA to the N-terminal amino acid of the target protein and results in the fatty acid being amide-bonded to the α-amino group of the amino acid. Because this transfer is susceptible to protein synthesis inhibitors, it must take place as the protein is synthesized (6,7). Data from the studies on both the sequence of known myristoylated proteins, and from those on the sequence requirements for NMT, suggests that the N-terminal amino acid is always a glycine residue (5). However the other sequence requirements for protein N-myristoylation are less certain and the resulting vague general consensus sequence is summarized in Fig. 1. Although the majority of proteins that are substrates for NMT are myristoylated, the enzyme can make use of a limited range of other fatty acids, including shorter-chain and unsaturated fatty acids. In general, this occurs when these fatty acids form the majority of the acyl-CoA pool in a cell or tissue, for example, in the retina (8). For most practical purposes, however, NMT can be regarded as essentially specific for myristic acid.