{"doi":"10.1038/s41586-018-0029-y","title":"Structural basis for ATP-dependent chromatin remodelling by the INO80 complex","abstract":"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 remodellers<sup>1-3</sup> such as the 15-subunit INO80 complex <sup>4</sup> . 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 DNA<sup>5-8</sup>. 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<sup>+</sup> 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 <sup>8</sup> 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.","journal":"Nature","year":2018,"id":4324,"datarank":0.844681767273205,"base_score":5.631211781821365,"endowment":5.631211781821365,"self_citation_contribution":0.844681767273205,"citation_network_contribution":0.0,"self_endowment_contribution":0.844681767273205,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":278,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0485,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2018-04-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":44681,"name":"Kevin Schall","orcid":"0000-0002-3417-0193","position":1,"is_corresponding":false},{"id":44682,"name":"Dirk Kostrewa","orcid":null,"position":2,"is_corresponding":false},{"id":44683,"name":"Kristina Lakomek","orcid":null,"position":3,"is_corresponding":false},{"id":44684,"name":"Mike Strauss","orcid":"0000-0002-0986-2868","position":4,"is_corresponding":false},{"id":44685,"name":"Manuela Moldt","orcid":null,"position":5,"is_corresponding":false},{"id":44687,"name":"K. Lakomek","orcid":null,"position":7,"is_corresponding":false},{"id":44688,"name":"Karl‐Peter Hopfner","orcid":"0000-0002-4528-8357","position":8,"is_corresponding":false},{"id":44680,"name":"Sebastian Eustermann","orcid":"0000-0002-4439-7770","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}