Conformational Switching of Arp5 Subunit Regulates INO80 Chromatin Remodeling

Authors

Shagun Shukla
Somnath Paul
Jeison Garcia
Yuan Zhong
Sara Sanz Juste
Karissa Beauchemin
Blaine Bartholomew

Publication Date

1-11-2025

Journal

Nucleic Acids Research

Abstract

The INO80 chromatin remodeler is a versatile enzyme capable of several functions, including spacing nucleosomes equal distances apart, precise positioning of nucleosomes based on DNA shape/sequence and exchanging histone dimers. Within INO80, the Arp5 subunit plays a central role in INO80 remodeling, evidenced by its interactions with the histone octamer, nucleosomal and extranucleosomal DNA, and its necessity in linking INO80's ATPase activity to nucleosome movement. We find two distinct regions of Arp5 binding near the acidic pocket of nucleosomes. One region has an arginine anchor that binds nucleosomes and is vital for INO80 mobilizing nucleosomes. The other region has a hydrophobic/acid patch of Leu and Asp that binds free histone H2A-H2B dimers. These two regions have different roles in remodeling nucleosomes as seen both in vitro and in vivo and the hydrophobic/acidic patch of Arp5 is likely needed for displacing DNA from the H2A-H2B surface and dimer exchange by INO80.

Keywords

Chromatin Assembly and Disassembly, Nucleosomes, Histones, Saccharomyces cerevisiae Proteins, Protein Conformation, Saccharomyces cerevisiae, Protein Subunits, Protein Binding, DNA, Models, Molecular

DOI

10.1093/nar/gkae1187

PMID

39676660

PMCID

PMC11754651

PubMedCentral® Posted Date

12-16-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes