9QQA

Ternary complex of translating ribosome, NAC and NMT1

This is a non-PDB format compatible entry.

Summary for 9QQA

• Entry DOI: 10.2210/pdb9qqa/pdb
• EMDB information: 53295
• Descriptor: 18S rRNA, Small ribosomal subunit protein uS2, 40S ribosomal protein S3a, ... (92 entities in total)
• Functional Keywords: translation, co-translational protein processing, ribosome
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 86
• Total formula weight: 3954487.11

Authors

Echeverria, B.,Jaskolowski, M.,Scaiola, A.,Ban, N. (deposition date: 2025-03-31, release date: 2025-07-16, Last modification date: 2025-07-23)

Primary citation

Gamerdinger, M.,Echeverria, B.,Lentzsch, A.M.,Burg, N.,Fan, Z.,Jaskolowski, M.,Scaiola, A.,Piening, S.,Shan, S.O.,Ban, N.,Deuerling, E.
Mechanism of cotranslational protein N-myristoylation in human cells.
Mol.Cell, 2025

PubMed 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 triggered by methionine excision, which exposes the N-myristoylation motif in the nascent chain. The revealed mode of interaction of NMT1 with NAC and the methionine-cleaved nascent protein elucidates how a specific subset of proteins can be efficiently N-myristoylated in human cells.

PubMed: 40639378
DOI: 10.1016/j.molcel.2025.06.015

Experimental method

ELECTRON MICROSCOPY (2.8 Å)