9qlq | pdb_00009qlq
NMT1-NAC bound human RNC with full length ARF1 - alternative State
Structural highlights
FunctionERF1_HUMAN Directs the termination of nascent peptide synthesis (translation) in response to the termination codons UAA, UAG and UGA. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons.[1] Publication Abstract from PubMedModifications of proteins occurring during translation are critical for protein localization, stability and function. N-myristoylation is an essential N-terminal lipid modification catalyzed co-translationally by N-myristoyltransferases (NMTs) which have been identified as promising drug targets. However, its molecular basis in the context of the translating ribosome is not known. Here, we reveal the structural basis for co-translational N-myristoylation by NMT1 on the human ribosome by cryo-electron microscopy (cryo-EM). We show that NMT1 binds near the peptide tunnel exit and interacts with the nascent polypeptide-associated complex (NAC). Unlike other multi-enzyme complexes that act simultaneously, we find that methionine excision by methionine aminopeptidases and N-myristoylation occur sequentially via consecutive binding to the ribosome. Furthermore, our data suggest that NMT1 remains associated with elongating nascent chains, indicating a co-translational chaperone-like function in partnership with NAC. These insights provide a molecular foundation for the understanding of the co-translational N-myristoylation mechanism in humans. Structural basis of co-translational N-myristoylation in humans.,Denk T, Monassa P, Musial J, Berninghausen O, Beatrix B, Giglione C, Meinnel T, Beckmann R Nat Commun. 2026 Jan 23;17(1):1191. doi: 10.1038/s41467-025-67962-4. PMID:41577716[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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