9I2D

NMT1-NAC bound human RNC with 10 amino acid ARF1-linker

This is a non-PDB format compatible entry.

Summary for 9I2D

• Entry DOI: 10.2210/pdb9i2d/pdb
• EMDB information: 52581
• Descriptor: CMV-staller mRNA with 18aa ARF1-linker, 60S ribosomal protein L4, 60S ribosomal protein L5, ... (91 entities in total)
• Functional Keywords: myristoylation, nmt1, co-translational, nac, ribosome, rnc
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 88
• Total formula weight: 4154063.19

Authors

Denk, T.,Berninghausen, O.,Beckmann, R. (deposition date: 2025-01-20, release date: 2026-02-04, Last modification date: 2026-02-18)

Primary citation

Denk, T.,Monassa, P.,Musial, J.,Berninghausen, O.,Beatrix, B.,Giglione, C.,Meinnel, T.,Beckmann, R.
Structural basis of co-translational N-myristoylation in humans.
Nat Commun, 17:1191-1191, 2026

PubMed Abstract: Modifications 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.

PubMed: 41577716
DOI: 10.1038/s41467-025-67962-4

Experimental method

ELECTRON MICROSCOPY (2.19 Å)