Mechanism of cotranslational protein N-myristoylation in human cells.

ABSTRACT: N-myristoyltransferases (NMTs) cotranslationally transfer the fatty acid myristic acid to the N terminus of newly synthesized proteins, regulating their function and cellular localization. These enzymes are important drug targets for the treatment of cancer and viral infections. N-myristoylation of nascent proteins occurs specifically on N-terminal glycine residues after the excision of the initiator methionine by methionine aminopeptidases (METAPs). How NMTs interact with ribosomes and gain timely and specific access to their substrates remains unknown. Here, we show that human NMT1 exchanges with METAP1 at the ribosomal tunnel exit to form an active cotranslational complex together with the nascent polypeptide-associated complex (NAC). NMT1 binding is sequence selective and specifically

SUBMITTER: Gamerdinger M 

PROVIDER: S-EPMC12863714 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature