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| Title | NAA40 and NAC cooperate in co-translational histone acetylation in humans. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 17, Issue 1, Year 2026 |
| Publish date | Mar 12, 2026 |
Authors | Dandan Guan / Timo Denk / Ariel Klavaris / Matthias Thoms / Otto Berninghausen / Birgitta Beatrix / Antonis Kirmizis / Roland Beckmann / ![]() |
| 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. ...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. |
External links | Nat Commun / PubMed:41820326 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.67 - 3.54 Å |
| Structure data | EMDB-55610, PDB-9t69: EMDB-55612, PDB-9t6c: EMDB-55613, PDB-9t6d: EMDB-55616, PDB-9t6i: |
| Chemicals | ![]() ChemComp-MG: ![]() ChemComp-ZN: ![]() ChemComp-HOH: |
| Source |
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Keywords | RIBOSOME / 80S / co-translational / NAA40 / NAC / histone acetylation / N-terminal acetylation / human |
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homo sapiens (human)
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