Myristoylated

Myristoylated describes a molecule, typically a protein, that bears a myristoyl group covalently attached to its N-terminal glycine residue through an amide bond. This modification, known as N-myristoylation, is most commonly co-translational, attaching the 14-carbon saturated fatty acid myristate from myristoyl-CoA to the α-amino group of the N-terminal glycine after the initiator methionine is removed.

The reaction is catalyzed by N-myristoyltransferase (NMT), which in many organisms exists as multiple isoforms (for example, human NMT1 and NMT2). The modification is irreversible and typically required soon after protein synthesis. The added myristoyl group increases the hydrophobicity of the protein, promoting association with membranes and influencing subcellular localization, stability, and interactions with other proteins. In many cases, myristoylation cooperates with other lipid modifications, such as palmitoylation, to regulate membrane targeting and signaling.

Biological significance is greatest in signaling proteins and in various viral and parasite proteins. Myristoylation can be essential for proper localization and function in some contexts, though some proteins remain functional without the modification. Prediction relies on the exposure of glycine at position 2 after methionine removal, but the recognition motif for NMT is variable, so experimental validation is common.

Detection and research methods include metabolic labeling with radiolabeled or bioorthogonal myristate analogs and mass spectrometry to confirm the modification. Bioinformatic predictions can suggest potential myristoylation sites, but they are not definitive without empirical confirmation.

Clinical and therapeutic relevance includes the exploration of NMT inhibitors as potential treatments for cancer and infectious diseases, given the reliance of certain pathogens and dysregulated cells on myristoylation for essential protein functions.