Myristoylation

Abstract

N-myristoylation is an acylation process absolutely specific to the N-terminal amino acid glycine in proteins. This maturation process concerns about a hundred proteins in lower and higher eukaryotes involved in oncogenesis, in secondary cellular signalling, in infectivity of retroviruses and, marginally, of other virus types. Thy cytosolic enzyme responsible for this activity, N-myristoyltransferase (NMT), studied since 1987, has been purified from different sources. However, the studies of the specificities of the various NMTs have not progressed in detail except for those relating to the yeast cytosolic enzyme. Still to be explained are differences in species specificity and between various putative isoenzymes, also whether the data obtained from the yeast enzyme can be transposed to other NMTs. The present review discusses data on the various addressing processes subsequent to myristoylation, a patchwork of pathways that suggests myristoylation is only the first step of the mechanisms by which a protein associates with the membrane. Concerning the enzyme itself, there are evidences that NMT is also present in the endoplasmic reticulum and that its substrate specificity is different from that of the cytosolic enzyme(s). These differences have major implications for their differential inhibition and for their respective roles in several pathologies. For instance, the NMTs from mammalians are clearly different from those found in several microorganisms, which raises the question whether the NMT may be a new targets for fungicides. Finally, since myristoylation has a central role in virus maturation and oncogenesis, specific NMT inhibitors might lead to potent antivirus and anticancer agents.

Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression

“…Processing of the initiator methionine residue is an evolutionarily conserved prerequisite step for different posttranslational protein modifications, such as N-terminal acetylation (25), protein subcellular localizations (26), and protein half-lives (27). Identification of HsMetAP1-specific inhibitors has shed light on the functions of type I MetAP in mammalian cells.…”

Optimized expression and purification of myristoylated human neuronal calcium sensor 1 in E. coli

“…Additionally, along with its many roles in NCS proteins, the myristoylation modification has been demonstrated to play a significant role in a number of important protein driven and larger pathological processes [35][36]. With a suitable method of detection of target protein myristoylation, it should be possible to extend this purification system to produce large quantities of myristoylated variants of other proteins.…”

Emerging roles for protein S-palmitoylation in Toxoplasma biology

“…Myristoylation and prenylation are irreversible and lead to a loose association with membranes. Protein myristoylation consists of the co-translational addition of a 14-carbon saturated fatty acid (myristate) to a N-terminal glycine (Boutin, 1997;Farazi et al, 2001), whereas prenylation post-translationally links a 15-(farnesyl) or 20-carbon (geranylgeranyl) isoprenoid to a C-terminal cysteine through a thioether bond (Zhang and Casey, 1996;Amaya et al, 2011) (Fig. 1A and B).…”