9T6C

NAA40-NAC bound active human 80S

This is a non-PDB format compatible entry.

Summary for 9T6C

• Entry DOI: 10.2210/pdb9t6c/pdb
• EMDB information: 55612
• Descriptor: 60S ribosomal protein L8, N-alpha-acetyltransferase 40, 28S ribosomal RNA, ... (89 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: 86
• Total formula weight: 3760382.99

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 (2.91 Å)