Structural basis for ATP-dependent chromatin remodelling by the INO80 complex

Nature. 2018 Apr;556(7701):386-390. doi: 10.1038/s41586-018-0029-y. Epub 2018 Apr 11.


In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers1-3 such as the 15-subunit INO80 complex 4 . INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and -1 nucleosomes at promoter DNA5-8. The structures and mechanisms of these remodelling reactions are currently unknown. Here we report the cryo-electron microscopy structure of the evolutionarily conserved core of the INO80 complex from the fungus Chaetomium thermophilum bound to a nucleosome, at a global resolution of 4.3 Å and with major parts at 3.7 Å. The INO80 core cradles one entire gyre of the nucleosome through multivalent DNA and histone contacts. An Rvb1/Rvb2 AAA+ ATPase heterohexamer is an assembly scaffold for the complex and acts as a 'stator' for the motor and nucleosome-gripping subunits. The Swi2/Snf2 ATPase motor binds to nucleosomal DNA at superhelical location -6, unwraps approximately 15 base pairs, disrupts the H2A-DNA contacts and is poised to pump entry DNA into the nucleosome. Arp5 and Ies6 bind superhelical locations -2 and -3 to act as a counter grip for the motor, on the other side of the H2A-H2B dimer. The Arp5 insertion domain forms a grappler element that binds the nucleosome dyad, connects the Arp5 actin-fold and entry DNA over a distance of about 90 Å and packs against histone H2A-H2B near the 'acidic patch'. Our structure together with biochemical data 8 suggests a unified mechanism for nucleosome sliding and histone editing by INO80. The motor is part of a macromolecular ratchet, persistently pumping entry DNA across the H2A-H2B dimer against the Arp5 grip until a large nucleosome translocation step occurs. The transient exposure of H2A-H2B by motor activity as well as differential recognition of H2A.Z and H2A may regulate histone exchange.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Chaetomium / enzymology*
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cryoelectron Microscopy*
  • DNA / chemistry
  • DNA / metabolism
  • DNA / ultrastructure
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism
  • DNA Helicases / ultrastructure*
  • Fungal Proteins
  • Histones / chemistry
  • Histones / metabolism
  • Histones / ultrastructure
  • Humans
  • Models, Molecular
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Multiprotein Complexes / ultrastructure*
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism*
  • Nucleosomes / ultrastructure
  • Protein Binding
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Structure-Activity Relationship


  • Chromosomal Proteins, Non-Histone
  • Fungal Proteins
  • Histones
  • INO80 complex, S cerevisiae
  • Multiprotein Complexes
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphate
  • DNA
  • DNA Helicases