Structural highlights
FunctionPublication Abstract from PubMedN-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. NAA40 and NAC cooperate in co-translational histone acetylation in humans.,Guan D, Denk T, Klavaris A, Thoms M, Berninghausen O, Beatrix B, Kirmizis A, Beckmann R Nat Commun. 2026 Mar 12;17(1):2486. doi: 10.1038/s41467-026-70279-5. PMID:41820326[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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