8ghl
From Proteopedia
the Hir complex core
Structural highlights
FunctionHIR3_YEAST HIR1, HIR2 and HIR3 are repressors of histone gene transcription. They are required for the periodic repression of three of the four histone gene loci during cell cycle as well as for autogenous regulation of the HTA1-HTB1 locus by H2A and H2B. Also has a role in nucleosome assembly.[1] [2] Publication Abstract from PubMedThe 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 A 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. Structure of the Hir histone chaperone complex.,Kim HJ, Szurgot MR, van Eeuwen T, Ricketts MD, Basnet P, Zhang AL, Vogt A, Sharmin S, Kaplan CD, Garcia BA, Marmorstein R, Murakami K Mol Cell. 2024 Jun 20:S1097-2765(24)00478-7. doi: 10.1016/j.molcel.2024.05.031. PMID:38925115[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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