Cryo-EM structures of the human INO80 chromatin-remodeling complex

Nat Struct Mol Biol. 2018 Jan;25(1):37-44. doi: 10.1038/s41594-017-0003-7. Epub 2017 Dec 4.

Abstract

Access to chromatin for processes such as transcription and DNA repair requires the sliding of nucleosomes along DNA. This process is aided by chromatin-remodeling complexes, such as the multisubunit INO80 chromatin-remodeling complex. Here we present cryo-EM structures of the active core complex of human INO80 at 9.6 Å, with portions at 4.1-Å resolution, and reconstructions of combinations of subunits. Together, these structures reveal the architecture of the INO80 complex, including Ino80 and actin-related proteins, which is assembled around a single RUVBL1 (Tip49a) and RUVBL2 (Tip49b) AAA+ heterohexamer. An unusual spoked-wheel structural domain of the Ino80 subunit is engulfed by this heterohexamer; both, in combination, form the core of the complex. We also identify a cleft in RUVBL1 and RUVBL2, which forms a major interaction site for partner proteins and probably communicates these interactions to its nucleotide-binding sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / chemistry*
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Chromatin / chemistry
  • Cryoelectron Microscopy*
  • Crystallography, X-Ray
  • DNA Helicases / chemistry*
  • DNA-Binding Proteins
  • Databases, Protein
  • Humans
  • Models, Molecular
  • Nucleosomes / metabolism
  • Protein Binding
  • Protein Domains
  • Protein Multimerization

Substances

  • Carrier Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Nucleosomes
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • INO80 protein, human
  • RUVBL1 protein, human
  • RUVBL2 protein, human