{"doi":"10.1093/nar/gkaa775","title":"Molecular determinants of MED1 interaction with the DNA bound VDR–RXR heterodimer","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The MED1 subunit of the Mediator complex is an essential coactivator of nuclear receptor-mediated transcriptional activation. While structural requirements for ligand-dependent binding of classical coactivator motifs of MED1 to numerous nuclear receptor ligand-binding domains have been fully elucidated, the recognition of the full-length or truncated coactivator by full nuclear receptor complexes remain unknown. Here we present structural details of the interaction between a large part of MED1 comprising its structured N-terminal and the flexible receptor-interacting domains and the mutual heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) bound to their cognate DNA response element. Using a combination of structural and biophysical methods we show that the ligand-dependent interaction between VDR and the second coactivator motif of MED1 is crucial for complex formation and we identify additional, previously unseen, interaction details. In particular, we identified RXR regions involved in the interaction with the structured N-terminal domain of MED1, as well as VDR regions outside the classical coactivator binding cleft affected by coactivator recruitment. These findings highlight important roles of each receptor within the heterodimer in selective recognition of MED1 and contribute to our understanding of the nuclear receptor-coregulator complexes.</jats:p>","journal":"Nucleic Acids Research","year":2020,"id":24564,"datarank":1.2000391239116381,"base_score":3.8501476017100584,"endowment":3.8501476017100584,"self_citation_contribution":0.5775221402565088,"citation_network_contribution":0.6225169836551292,"self_endowment_contribution":0.5775221402565088,"citer_contribution":0.6225169836551292,"corpus_percentile":null,"corpus_rank":null,"citation_count":46,"citer_count":28,"citers_with_citation_signal":22,"citers_with_endowment":22,"datacite_reuse_total":14,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":142790,"name":"Maxime Bourguet","orcid":null,"position":1,"is_corresponding":false},{"id":142791,"name":"Steve Hessmann","orcid":null,"position":2,"is_corresponding":false},{"id":142792,"name":"Sandra Chalhoub","orcid":null,"position":3,"is_corresponding":false},{"id":142793,"name":"Bruno Kieffer","orcid":"0000-0002-2033-4679","position":4,"is_corresponding":false},{"id":142794,"name":"Sarah Cianférani","orcid":"0000-0003-4013-4129","position":5,"is_corresponding":false},{"id":142795,"name":"Natacha Rochel","orcid":"0000-0002-3573-5889","position":6,"is_corresponding":false},{"id":142789,"name":"Anna Y. Belorusova","orcid":"0000-0002-5229-4536","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.8501476017100584,"endowment":3.8501476017100584,"datacite_reuse_total":14,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32990725","pmcid":"PMC7641746","openalex_id":"https://openalex.org/W3089424026","authors":[],"funders":[{"funder_name":"Agence Nationale de la Recherche","grant_id":"ANR-13-BSV8-0024-01","title":null},{"funder_name":"Agence Nationale de la Recherche","grant_id":"ANR-10-IDEX-0002-02","title":null},{"funder_name":"French Infrastructure for Integrated Structural Biology","grant_id":"ANR-10-INBS-05","title":null},{"funder_name":"French Infrastructure for Integrated Structural Biology","grant_id":"ANR-10-LABX-0030-INRT","title":null},{"funder_name":"French Proteomic Infrastructure","grant_id":"ANR-10-INBS-08-03","title":null},{"funder_name":"FRM","grant_id":"FDT20140930978","title":null},{"funder_name":"French National Research Agency (ANR)","grant_id":"ANR-10-LABX-0030","title":null},{"funder_name":"French National Research Agency (ANR)","grant_id":"ANR-10-IDEX-0002","title":null},{"funder_name":"French National Research Agency (ANR)","grant_id":"ANR-13-BSV8-0024","title":"Characterization through an integrative biology approach of Vitamin D signaling to identify novel therapeutic molecules"}],"total_grants":9,"fwci":2.7506,"citation_percentile":0.91411661,"influential_citations":2,"citation_trend":[{"year":2020,"count":1},{"year":2021,"count":22},{"year":2022,"count":6},{"year":2023,"count":4},{"year":2024,"count":5},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://academic.oup.com/nar/article-pdf/48/19/11199/34133416/gkaa775.pdf","host_type":"journal"},{"url":"https://academic.oup.com/nar/article-pdf/48/19/11199/34133416/gkaa775.pdf","host_type":"GREEN"},{"url":"https://academic.oup.com/nar/article-pdf/48/19/11199/34133416/gkaa775.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/nar/article-pdf/48/19/11199/34133416/gkaa775.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/nar/gkaa775","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32990725","host_type":"repository"},{"url":"https://hal.science/hal-02962412","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7641746","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7641746","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7641746?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/2020.06.17.157305","host_type":""},{"url":"http://dx.doi.org/10.1093/nar/gkaa775","host_type":""},{"url":"https://epn-library.esrf.fr/flora/jsp/index_view_direct_anonymous.jsp?record=doc:PUB_ESRF:56487","host_type":""},{"url":"https://dx.doi.org/10.1101/2020.06.17.157305","host_type":""},{"url":"https://dx.doi.org/10.1093/nar/gkaa775","host_type":""},{"url":"https://hal.science/hal-02962412v1","host_type":""},{"url":"https://hal.science/hal-02962412v1/document","host_type":""},{"url":"https://doi.org/https://doi.org/10.1093/nar/gkaa775","host_type":""}],"fields_of_study":["Retinoids in leukemia and cellular processes","Genomics and Chromatin Dynamics","RNA Research and Splicing","Biology","Chemistry","Medicine","0301 basic medicine","0303 health sciences","03 medical and health sciences","DNA","Humans","Ligands","Mediator Complex Subunit 1","Protein Binding","Protein Domains","Protein Multimerization","Receptors, Calcitriol","Retinoid X Receptor alpha"],"mesh_terms":["Protein Domains","DNA","Humans","Ligands","Protein Binding","Receptors, Calcitriol","Retinoid X Receptor alpha","Protein Multimerization","Mediator Complex Subunit 1"],"keywords":["Biology","Calcitriol receptor","DNA","Genetics","DNA-binding protein","Retinoid X receptor","Transcription factor","Cell biology","Computational biology","Biochemistry","Gene","Nuclear receptor","570","Retinoid X Receptor alpha","[SDV]Life Sciences [q-bio]","540","Ligands","[SDV] Life Sciences [q-bio]","Mediator Complex Subunit 1","Protein Domains","Structural Biology","Humans","Receptors, Calcitriol","Protein 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