{"doi":"10.1101/2021.11.25.469965","title":"Molecular architecture of nucleosome remodeling and deacetylase sub-complexes by integrative structure determination","abstract":"Abstract The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin-modifying assembly that regulates gene expression and DNA damage repair. Despite its importance, limited structural information describing the complete NuRD complex is available and a detailed understanding of its mechanism is therefore lacking. Drawing on information from SEC-MALLS, DIA-MS, XLMS, negative-stain EM, X-ray crystallography, NMR spectroscopy, secondary structure predictions and homology models, we applied Bayesian integrative structure determination to investigate the molecular architecture of three NuRD sub-complexes: MTA1-HDAC1-RBBP4 (MHR), MTA1 N -HDAC1-MBD3 GATAD2CC (MHM), and MTA1-HDAC1-RBBP4-MBD3-GATAD2A (NuDe). The integrative structures were corroborated by examining independent crosslinks, cryo-EM maps, biochemical assays, known cancer-associated mutations, and structure predictions from AlphaFold. The robustness of the models was assessed by jack-knifing. Localization of the full-length MBD3, which connects the deacetylase and chromatin remodeling modules in NuRD, has not previously been possible; our models indicate two different locations for MBD3, suggesting a mechanism by which MBD3 in the presence of GATAD2A asymmetrically bridges the two modules in NuRD. Further, our models uncovered three previously unrecognized subunit interfaces in NuDe: HDAC1 C -MTA1 BAH , MTA1 BAH -MBD3 MBD , and HDAC1 60-100 -MBD3 MBD . Our approach also allowed us to localize regions of unknown structure, such as HDAC1 C and MBD3 IDR , thereby resulting in the most complete and robustly cross-validated structural characterization of these NuRD sub-complexes so far.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":222055,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9094,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308204,"name":"Matthew J. Jackman","orcid":"0000-0001-7464-5694","position":1,"is_corresponding":false},{"id":308197,"name":"Jason K. K. Low","orcid":"0000-0003-0862-0012","position":2,"is_corresponding":false},{"id":308208,"name":"Michael J. Landsberg","orcid":"0000-0002-2464-990X","position":3,"is_corresponding":false},{"id":78312,"name":"Joel P. Mackay","orcid":"0000-0001-7508-8033","position":4,"is_corresponding":false},{"id":565815,"name":"Shruthi Viswanath","orcid":"0000-0002-9061-8407","position":5,"is_corresponding":false},{"id":822716,"name":"Shreyas Arvindekar","orcid":"0000-0002-9945-8534","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-18T23:53:59.302331Z","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":[]}