The nuclear actin-containing Arp8 module is a linker DNA sensor driving INO80 chromatin remodeling

Nat Struct Mol Biol. 2018 Sep;25(9):823-832. doi: 10.1038/s41594-018-0115-8. Epub 2018 Sep 3.

Abstract

Nuclear actin (N-actin) and actin-related proteins (Arps) are critical components of several chromatin modulating complexes, including the chromatin remodeler INO80, but their function is largely elusive. Here, we report the crystal structure of the 180-kDa Arp8 module of Saccharomyces cerevisiae INO80 and establish its role in recognition of extranucleosomal linker DNA. Arp8 engages N-actin in a manner distinct from that of other actin-fold proteins and thereby specifies recruitment of the Arp4-N-actin heterodimer to a segmented scaffold of the helicase-SANT-associated (HSA) domain of Ino80. The helical HSA domain spans over 120 Å and provides an extended binding platform for extranucleosomal entry DNA that is required for nucleosome sliding and genome-wide nucleosome positioning. Together with the recent cryo-electron microscopy structure of INO80Core-nucleosome complex, our findings suggest an allosteric mechanism by which INO80 senses 40-bp linker DNA to conduct highly processive chromatin remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Nucleus / metabolism*
  • Chromatin Assembly and Disassembly*
  • DNA, Fungal / metabolism*
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism*
  • Protein Conformation
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Homology, Amino Acid

Substances

  • ARP8 protein, S cerevisiae
  • DNA, Fungal
  • INO80 complex, S cerevisiae
  • Microfilament Proteins
  • Saccharomyces cerevisiae Proteins