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TitleMechanism of cotranslational modification of histones H2A and H4 by MetAP1 and NatD.
Journal, issue, pagesSci Adv, Vol. 11, Issue 51, Page eaeb1017, Year 2025
Publish dateDec 19, 2025
AuthorsDenis Yudin / Mateusz Jaskolowski / Ziyi Fan / Nicolas Burg / Sowmya Chandrasekar / Alfred M Lentzsch / Alain Scaiola / Adrian Bothe / Elke Deuerling / Martin Gamerdinger / Shu-Ou Shan / Nenad Ban /
PubMed AbstractThe replication-dependent histones H2A and H4 are among the most highly expressed proteins in eukaryotes during the S phase to ensure packaging of replicated chromosomes. Nearly all newly synthesized ...The replication-dependent histones H2A and H4 are among the most highly expressed proteins in eukaryotes during the S phase to ensure packaging of replicated chromosomes. Nearly all newly synthesized H2A and H4 are N-terminally acetylated by N-terminal acetyltransferase D (NatD) following excision of the initiator methionine by methionine aminopeptidases (MetAPs). These modifications influence chromatin function, but how they occur cotranslationally on these exceptionally abundant and small proteins was not understood. Here, we show that the nascent polypeptide-associated complex controls the cotranslational modification of histones H2A and H4 by recruiting NatD and the upstream enzyme MetAP1 to ribosomes. MetAP1 and NatD cooperate on the ribosome to create a confined environment for the efficient sequential modification of the nascent histone chain. Our work provides a mechanistic model for the early steps of histone maturation.
External linksSci Adv / PubMed:41417911 / PubMed Central
MethodsEM (single particle)
Resolution3.55 Å
Structure data

55351

9syr

EMDB-55351, PDB-9syr:
Human quaternary complex of a translating 80S ribosome, NAC, MetAP1 and NatD
Method: EM (single particle) / Resolution: 3.55 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-COA:
COENZYME A

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

Source
  • homo sapiens (human)
  • saccharomyces cerevisiae s288c (yeast)
  • aequorea victoria (jellyfish)
  • brachypodium distachyon (stiff brome)
KeywordsRIBOSOME / translation / NAC / N-terminal acetyltransferase / NatD / MetAP1

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