6VZ4

Cryo-EM structure of Sth1-Arp7-Arp9-Rtt102 bound to the nucleosome in ADP Beryllium Fluoride state

Summary for 6VZ4

• Entry DOI: 10.2210/pdb6vz4/pdb
• EMDB information: 21484
• Descriptor: Histone H3, Regulator of Ty1 transposition protein 102, MAGNESIUM ION, ... (14 entities in total)
• Functional Keywords: chromatin remodeling, nucleosome, gene regulation, motor protein
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 14
• Total formula weight: 444625.28

Authors

Leschziner, A.E.,Baker, R.W. (deposition date: 2020-02-27, release date: 2020-12-02, Last modification date: 2024-03-06)

Primary citation

Baker, R.W.,Reimer, J.M.,Carman, P.J.,Turegun, B.,Arakawa, T.,Dominguez, R.,Leschziner, A.E.
Structural insights into assembly and function of the RSC chromatin remodeling complex.
Nat.Struct.Mol.Biol., 28:71-80, 2021

PubMed 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.

PubMed: 33288924
DOI: 10.1038/s41594-020-00528-8

Experimental method

ELECTRON MICROSCOPY (3.9 Å)