9T69

In vitro reconstituted METAP1-NAA40-NAC bound 80S - State 1

This is a non-PDB format compatible entry.

Summary for 9T69

• Entry DOI: 10.2210/pdb9t69/pdb
• EMDB information: 55610
• Descriptor: 28S rRNA, 60S ribosomal protein L7a, 60S ribosomal protein L9, ... (88 entities in total)
• Functional Keywords: 80s, ribosome, co-translational, naa40, nac, histone acetylation, n-terminal acetylation, human
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 85
• Total formula weight: 3958512.89

Authors

Guan, D.,Berninghausen, O.,Beckmann, R. (deposition date: 2025-11-07, release date: 2026-09-30)

Primary citation

Guan, D.,Denk, T.,Klavaris, A.,Thoms, M.,Berninghausen, O.,Beatrix, B.,Kirmizis, A.,Beckmann, R.
NAA40 and NAC cooperate in co-translational histone acetylation in humans.
Nat Commun, 17:-, 2026

PubMed Abstract: N-terminal acetylation is an abundant and predominantly co-translational modification in eukaryotes that profoundly affects folding, compartmentalization fidelity and turnover of target proteins. Unlike other N-acetyltransferases, human NatD is composed solely of the catalytic subunit NAA40 and exclusively modifies histone proteins H2A and H4. However, the molecular details of co-translational NAA40 activity have remained elusive. Here, we show biochemically and by cryo-EM how NAA40 activity is coordinated at the ribosomal peptide tunnel exit involving the NAC complex. We demonstrate that the NAA40-NAC interaction is required for efficient ribosome binding and histone acetylation. Furthermore, we provide insights on the potential coordination of methionine removal and subsequent NAA40-mediated acetylation by formation of a multienzyme complex on the ribosome involving METAP1. Therefore, our results illustrate the details of N-terminal histone acetylation by NAA40 and highlight the role of NAC as a general coordinator of nascent protein modification.

PubMed: 41820326
DOI: 10.1038/s41467-026-70279-5

Experimental method

ELECTRON MICROSCOPY (3.54 Å)