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TitleStructural insights into histone exchange by human SRCAP complex.
Journal, issue, pagesCell Discov, Vol. 10, Issue 1, Page 15, Year 2024
Publish dateFeb 8, 2024
AuthorsJiali Yu / Fengrui Sui / Feng Gu / Wanjun Li / Zishuo Yu / Qianmin Wang / Shuang He / Li Wang / Yanhui Xu /
PubMed AbstractHistone variant H2A.Z is found at promoters and regulates transcription. The ATP-dependent chromatin remodeler SRCAP complex (SRCAP-C) promotes the replacement of canonical histone H2A-H2B dimer with ...Histone variant H2A.Z is found at promoters and regulates transcription. The ATP-dependent chromatin remodeler SRCAP complex (SRCAP-C) promotes the replacement of canonical histone H2A-H2B dimer with H2A.Z-H2B dimer. Here, we determined structures of human SRCAP-C bound to H2A-containing nucleosome at near-atomic resolution. The SRCAP subunit integrates a 6-subunit actin-related protein (ARP) module and an ATPase-containing motor module. The ATPase-associated ARP module encircles half of the nucleosome along the DNA and may restrain net DNA translocation, a unique feature of SRCAP-C. The motor module adopts distinct nucleosome binding modes in the apo (nucleotide-free), ADP-bound, and ADP-BeF-bound states, suggesting that ATPase-driven movement destabilizes H2A-H2B by unwrapping the entry DNA and pulls H2A-H2B out of nucleosome through the ZNHIT1 subunit. Structure-guided chromatin immunoprecipitation sequencing analysis confirmed the requirement of H2A-contacting ZNHIT1 in maintaining H2A.Z occupancy on the genome. Our study provides structural insights into the mechanism of H2A-H2A.Z exchange mediated by SRCAP-C.
External linksCell Discov / PubMed:38331872 / PubMed Central
MethodsEM (single particle)
Resolution3.2 Å
Structure data

EMDB-37984, PDB-8x15:
Structure of nucleosome-bound SRCAP-C in the apo state
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-37988, PDB-8x19:
Structure of nucleosome-bound SRCAP-C in the ADP-BeFx-bound state
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-37990, PDB-8x1c:
Structure of nucleosome-bound SRCAP-C in the ADP-bound state
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN/DNA / Remodeler; SRCAP; H2A.Z / DNA BINDING PROTEIN-DNA complex

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