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TitleSubnucleosome preference of human chromatin remodeller SMARCAD1.
Journal, issue, pagesNature, Vol. 644, Issue 8077, Page 818-826, Year 2025
Publish dateJun 4, 2025
AuthorsPengjing Hu / Jingxi Sun / Hongyao Sun / Kangjing Chen / Youyang Sia / Xian Xia / Qiaoran Xi / Zhucheng Chen /
PubMed AbstractChromatin remodellers are pivotal in the regulation of nucleosome dynamics in cells, and they are important for chromatin packaging, transcription, replication and DNA repair. Here we show that the ...Chromatin remodellers are pivotal in the regulation of nucleosome dynamics in cells, and they are important for chromatin packaging, transcription, replication and DNA repair. Here we show that the human chromatin remodeller SMARCAD1 exhibits a substrate preference for subnucleosomal particles over the canonical nucleosome. Cryo-electron microscopy structures of SMARCAD1 bound to the nucleosome and hexasome provide mechanistic insights into the substrate selectivity. SMARCAD1 binds to the hexasome through multiple family-specific elements that are essential for the functions in vitro and in cells. The enzyme binds to the canonical nucleosome in an inactive conformation, which accounts for its diminished activity towards the nucleosome. Notably, the histone chaperone FACT complex acts synergistically with H2A-H2B to promote the activity of SMARCAD1 in nucleosome remodelling. Together, our findings reveal an avenue for chromatin regulation, whereby subnucleosomes are remodelled through an ATP-dependent process.
External linksNature / PubMed:40468067
MethodsEM (single particle)
Resolution2.9 - 3.7 Å
Structure data

EMDB-61295: The motor of SMARCAD1 bound on hexasome
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-61296, PDB-9jao:
The structure of SMARCAD1 bound to the hexasome in the presence of ADP-BeFx
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-61297: The structure of SMARCAD1 bound to the nucleosome in the presence of ADP-BeFx.
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-61298: The structure of SMARCAD1 bound to the nucleosome in Apo state.
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

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

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN/DNA / DNA / ligand / protein / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex

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