Several hundred viral and cellular proteins have been shown to be covalently modified by fatty acids (1 –3 ). The two most common modifications, myristoylatron and palmitoylatron, differ with respect to the type and chemical nature of fatty acid attachment to the polypeptide backbone. Most proteins destined to become N-myrrstoylated contain the sequence: Met-Gly-X-X-X-Ser/Thr at their N-terminn. After the initrating methionine is removed, the 14-carbon fatty acid myristate is attached via amide linkage to the N-terminal glycme residue. The reaction occurs cotranslationally and is catalyzed by the soluble enzyme N-myristoyl transferase (NMT). NMT exhibits strict specificity for an N-terminal glycine and mutation of this glycine to alanme abrogates myristoylation. In contrast, palmitoylated proteins contam the 16-carbon fatty acid palintiate attached via throester linkage to one or more cysteme residues. Palmitoylation is a posttranslational reactron that appears to be mediated by a membrane-bound palmitoyl acyl transferase. Unlike myristoylation, whrch is generally a relatively stable modification, palmitoylatron can be reversed by the action of thioesterases. Dynamic palmitoylation has recently been shown to play key roles in the regulation of protein localization and function.
