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Structural insights into assembly and function of the RSC chromatin remodeling complex.
- Source :
-
Nature structural & molecular biology [Nat Struct Mol Biol] 2021 Jan; Vol. 28 (1), pp. 71-80. Date of Electronic Publication: 2020 Dec 07. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Amino Acid Sequence
Carrier Proteins metabolism
Cell Cycle Proteins metabolism
Chromosomal Proteins, Non-Histone metabolism
Cryoelectron Microscopy
Nuclear Proteins metabolism
Nucleosomes metabolism
Saccharomyces cerevisiae genetics
Chromatin metabolism
Chromatin Assembly and Disassembly physiology
DNA-Binding Proteins metabolism
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1545-9985
- Volume :
- 28
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature structural & molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 33288924
- Full Text :
- https://doi.org/10.1038/s41594-020-00528-8