{"doi":"10.1101/2020.05.05.079277","title":"Structural basis for heme-dependent NCoR binding to the transcriptional repressor REV-ERBβ","abstract":"ABSTRACT Heme is the endogenous ligand for the constitutively repressive REV-ERB nuclear receptors, REV-ERBα (NR1D1) and REV-ERBβ (NR1D2), but how heme regulates REV-ERB activity remains unclear. While cellular studies indicate heme is required for the REV-ERBs to bind the corepressor NCoR and repress transcription, fluorescence-based biochemical assays and crystal structures suggest that heme displaces NCoR. Here, we show that heme artifactually influences detection of NCoR interaction in fluorescence-based assays. However, using fluorescence-independent methods, isothermal titration calorimetry and NMR spectroscopy, we demonstrate that heme directly increases REV-ERBβ ligand-binding domain (LBD) binding affinity for NCoR. We further report two crystal structures of REV-ERBβ LBD cobound to heme and NCoR peptides, which reveal the structural basis for heme-dependent NCoR binding to REV-ERBβ. By resolving previous contradictory biochemical, structural, and cellular studies, our findings should facilitate renewed progress toward understanding heme-dependent REV-ERB activity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124873,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9454,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":282823,"name":"Jinsai Shang","orcid":"0000-0001-8164-1544","position":1,"is_corresponding":false},{"id":343815,"name":"Paola Munoz‐Tello","orcid":"0000-0002-5225-1907","position":2,"is_corresponding":false},{"id":282829,"name":"Douglas J. Kojetin","orcid":"0000-0001-8058-6168","position":3,"is_corresponding":false},{"id":282824,"name":"Sarah A. Mosure","orcid":"0000-0003-4477-5396","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:15:11.632153Z","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":[]}