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Structure paper

TitleStructural insights into assembly and function of the RSC chromatin remodeling complex.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 1, Page 71-80, Year 2021
Publish dateDec 7, 2020
AuthorsRichard W Baker / Janice M Reimer / Peter J Carman / Bengi Turegun / Tsutomu Arakawa / Roberto Dominguez / Andres E Leschziner /
PubMed AbstractSWI/SNF chromatin remodelers modify the position and spacing of nucleosomes and, in humans, are linked to cancer. To provide insights into the assembly and regulation of this protein family, we ...SWI/SNF chromatin remodelers modify the position and spacing of nucleosomes and, in humans, are linked to cancer. To provide insights into the assembly and regulation of this protein family, we focused on a subcomplex of the Saccharomyces cerevisiae RSC comprising its ATPase (Sth1), the essential actin-related proteins (ARPs) Arp7 and Arp9 and the ARP-binding protein Rtt102. Cryo-EM and biochemical analyses of this subcomplex shows that ARP binding induces a helical conformation in the helicase-SANT-associated (HSA) domain of Sth1. Surprisingly, the ARP module is rotated 120° relative to the full RSC about a pivot point previously identified as a regulatory hub in Sth1, suggesting that large conformational changes are part of Sth1 regulation and RSC assembly. We also show that a conserved interaction between Sth1 and the nucleosome acidic patch enhances remodeling. As some cancer-associated mutations dysregulate rather than inactivate SWI/SNF remodelers, our insights into RSC complex regulation advance a mechanistic understanding of chromatin remodeling in disease states.
External linksNat Struct Mol Biol / PubMed:33288924 / PubMed Central
MethodsEM (single particle)
Resolution3.9 - 4.3 Å
Structure data

21484

6vz4

EMDB-21484, PDB-6vz4:
Cryo-EM structure of Sth1-Arp7-Arp9-Rtt102 bound to the nucleosome in ADP Beryllium Fluoride state
Method: EM (single particle) / Resolution: 3.9 Å

21489

6vzg

EMDB-21489: cryo-EM structure of Sth1-Arp7-Arp9-Rtt102
PDB-6vzg: Cryo-EM structure of Sth1-Arp7-Arp9-Rtt102
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-21493:
cryo-EM map of Sth1-Arp7-Arp9-Rtt102 in the ADP BeF3 state bound to the nucleosome with a peeled DNA conformation
Method: EM (single particle) / Resolution: 4.3 Å

Chemicals

ChemComp-MG:
Unknown entry

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

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

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

Source
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsMOTOR PROTEIN / Chromatin remodeling / Nucleosome / Gene Regulation

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