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TitleStructure of the Hir histone chaperone complex.
Journal, issue, pagesMol Cell, Vol. 84, Issue 14, Page 2601-2617.e12, Year 2024
Publish dateJul 25, 2024
AuthorsHee Jong Kim / Mary R Szurgot / Trevor van Eeuwen / M Daniel Ricketts / Pratik Basnet / Athena L Zhang / Austin Vogt / Samah Sharmin / Craig D Kaplan / Benjamin A Garcia / Ronen Marmorstein / Kenji Murakami /
PubMed AbstractThe evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4) tetramers on DNA for replication-independent chromatin assembly. The ...The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4) tetramers on DNA for replication-independent chromatin assembly. The molecular architecture of the HIRA/Hir complex and its mode of histone deposition have remained unknown. Here, we report the cryo-EM structure of the S. cerevisiae Hir complex with Asf1/H3/H4 at 2.9-6.8 Å resolution. We find that the Hir complex forms an arc-shaped dimer with a Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4. The core of the complex containing two Hir1/Hir2/Hir2 trimers and N-terminal segments of Hir3 forms a central cavity containing two copies of Hpc2, with one engaged by Asf1/H3/H4, in a suitable position to accommodate a histone (H3/H4) tetramer, while the C-terminal segments of Hir3 harbor nucleic acid binding activity to wrap DNA around the Hpc2-assisted histone tetramer. The structure suggests a model for how the Hir/Asf1 complex promotes the formation of histone tetramers for their subsequent deposition onto DNA.
External linksMol Cell / PubMed:38925115 / PubMed Central
MethodsEM (single particle)
Resolution2.96 - 12 Å
Structure data

EMDB-40006: Hir complex core
PDB-8ghl: the Hir complex core
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-40029: Hir3 Arm/Tail, Hir2 WD40, Hpc2 C-term
PDB-8gha: Hir3 Arm/Tail, Hir2 WD40, C-terminal Hpc2
Method: EM (single particle) / Resolution: 6.8 Å

EMDB-40030, PDB-8ghm:
Hir1 WD40 domains and Asf1/H3/H4
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-40037: Composite map of the Hir complex with Asf1/H3/H4
PDB-8ghn: Composite model of the yeast Hir Complex with Asf1/H3/H4
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-40078, PDB-8gix:
Chaetomium thermophilum Hir3
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

ChemComp-TCE:
3,3',3''-phosphanetriyltripropanoic acid

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • Thermochaetoides thermophila (fungus)
  • thermochaetoides thermophila dsm 1495 (fungus)
KeywordsCHAPERONE / Histone / Complex / Replication-Independent / subunit

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