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TitleStructural basis of cotranslational protein N-terminal acetylation by NatB in human cells.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateJul 11, 2026
AuthorsNatalia Silva Alves / Pawel Knejski / Alain Scaiola / Marc Leibundgut / Martin Gamerdinger / Nenad Ban / Elke Deuerling /
PubMed AbstractCotranslational N-terminal acetylation is a widespread modification that shapes protein stability, localization, and function in eukaryotic cells. The essential human NatB complex (NAA25-NAA20) ...Cotranslational N-terminal acetylation is a widespread modification that shapes protein stability, localization, and function in eukaryotic cells. The essential human NatB complex (NAA25-NAA20) acetylates the initiator methionine of a substantial fraction of the proteome, yet how NatB engages translating ribosomes has remained unclear. Here we define the cotranslational mechanism underlying NatB function. NatB is recruited by the nascent polypeptide-associated complex (NAC) through a high-affinity interaction between the NACα UBA domain and the auxiliary subunit NAA25, while both NatB subunits form additional contacts with the ribosomal surface near the tunnel exit. Together, these interactions position the NatB active site directly adjacent to the emerging nascent chain, enabling efficient modification of newly synthesized proteins. Structural comparisons reveal a conserved ribosome-binding architecture shared with other N-acetyltransferases, including NatA/E and NatD, implying mutually exclusive ribosome occupancy. Together with prior work, these findings establish NAC as a central organizer of cotranslational N-terminal processing.
External linksNat Commun / PubMed:42436108 / PubMed Central
MethodsEM (single particle)
Resolution3.2 Å
Structure data

EMDB-57771, PDB-30hi:
Ternary complex of translating ribosome, NAC and NatB
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-ZN:
Unknown entry

ChemComp-COA:
COENZYME A

Source
  • homo sapiens (human)
KeywordsTRANSLATION / Cotranslational N-terminal acetylation / N-terminal acetyltransferase B (NaTB) / nascent polypeptide-associated complex (NAC) / translating ribosome

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