Reference: Kim HJ, et al. (2024) Structure of the Hir histone chaperone complex. Mol Cell 84(14):2601-2617.e12

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Abstract


The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4)2 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)2 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.

Reference Type
Journal Article
Authors
Kim HJ, Szurgot MR, van Eeuwen T, Ricketts MD, Basnet P, Zhang AL, Vogt A, Sharmin S, Kaplan CD, Garcia BA, ... Show all
Primary Lit For
HHF1 | HHT1 | HIR3 | HIR1 | HPC2 | ASF1 | HHF2 | HHT2 | HIR2 | HIR complex

Interaction Annotations


Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 24 entries for 7 genes

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InteractorInteractorAssayAnnotationActionModification
ASF1HIR2Affinity Capture-MSmanually curatedBait-HitNo Modification
HHF1ASF1Affinity Capture-MSmanually curatedHit-BaitNo Modification
HHF1HHT1Affinity Capture-MSmanually curatedHit-BaitNo Modification
HHF1HIR2Affinity Capture-MSmanually curatedBait-HitNo Modification
HHF1HIR3Affinity Capture-MSmanually curatedBait-HitNo Modification
HHT1ASF1Affinity Capture-MSmanually curatedHit-BaitNo Modification
HHT1HIR2Affinity Capture-MSmanually curatedBait-HitNo Modification
HHT1HIR3Affinity Capture-MSmanually curatedBait-HitNo Modification
HHT1HPC2Affinity Capture-MSmanually curatedBait-HitNo Modification
HIR1HIR2Affinity Capture-Westernmanually curatedBait-HitNo Modification
Showing 1 to 10 of 24 entries