9s3d
NAC bound human RNC with 58 amino acid ARF1-linker
Structural highlights
FunctionNACA_HUMAN Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites). May act as a specific coactivator for JUN, binding to DNA and stabilizing the interaction of JUN homodimers with target gene promoters.[1] [2] [3] 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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