Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 05 2023
27 05 2023
Historique:
received:
21
12
2022
accepted:
11
05
2023
medline:
29
5
2023
pubmed:
28
5
2023
entrez:
27
5
2023
Statut:
epublish
Résumé
The Rpd3L histone deacetylase (HDAC) complex is an ancient 12-subunit complex conserved in a broad range of eukaryotes that performs localized deacetylation at or near sites of recruitment by DNA-bound factors. Here we describe the cryo-EM structure of this prototypical HDAC complex that is characterized by as many as seven subunits performing scaffolding roles for the tight integration of the only catalytic subunit, Rpd3. The principal scaffolding protein, Sin3, along with Rpd3 and the histone chaperone, Ume1, are present in two copies, with each copy organized into separate lobes of an asymmetric dimeric molecular assembly. The active site of one Rpd3 is completely occluded by a leucine side chain of Rxt2, while the tips of the two lobes and the more peripherally associated subunits exhibit varying levels of flexibility and positional disorder. The structure reveals unexpected structural homology/analogy between unrelated subunits in the fungal and mammalian complexes and provides a foundation for deeper interrogations of structure, biology, and mechanism of these complexes, as well as for the discovery of HDAC complex-specific inhibitors.
Identifiants
pubmed: 37244892
doi: 10.1038/s41467-023-38687-z
pii: 10.1038/s41467-023-38687-z
pmc: PMC10224958
doi:
Substances chimiques
Transcription Factors
0
Repressor Proteins
0
Saccharomyces cerevisiae Proteins
0
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3061Subventions
Organisme : NCI NIH HHS
ID : P01 CA092584
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM135651
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM144559
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NIH HHS
ID : S10 OD025194
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM108569
Pays : United States
Organisme : NIGMS NIH HHS
ID : U24 GM129547
Pays : United States
Informations de copyright
© 2023. The Author(s).
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