{"doi":"10.1093/nar/gkaf1003","title":"The multimerization pathway of the glucocorticoid receptor","abstract":"The glucocorticoid receptor (GR) is a leading drug target due to its antiinflammatory and immunosuppressive roles. The functional oligomeric conformation of full-length GR (FL-GR), which is key for its biological activity, remains disputed. Here we present a new crystal structure of agonist-bound GR ligand-binding domain (GR-LBD) comprising eight copies of a noncanonical dimer. We verified the biological relevance of this dimer for receptor multimerization in wild-type and selected FL-GR mutants using molecular dynamics and crosslinking-mass spectrometry together with fluorescence microscopy and transcriptomic analysis in living cells. Self-association of this GR-LBD basic dimer in two mutually exclusive assemblies reveals clues for FL-GR multimerization and activity in cells. We propose a model for the structure of multidomain GR based on our new data and suggest a detailed oligomerization pathway. This model reconciles all currently available structural and functional information and provides a more comprehensive understanding of the rare disorder, generalized glucocorticoid resistance.","journal":"Nucleic Acids Research","year":2025,"id":522249,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":565976,"name":"Alba Jiménez‐Panizo","orcid":"0000-0001-7046-6162","position":1,"is_corresponding":false},{"id":1394237,"name":"Agustina L. Lafuente","orcid":null,"position":2,"is_corresponding":false},{"id":628073,"name":"Thomas A. Johnson","orcid":"0000-0002-9135-3252","position":3,"is_corresponding":false},{"id":1393692,"name":"Inés Montoya-Novoa","orcid":"0009-0005-1369-7382","position":4,"is_corresponding":false},{"id":1393693,"name":"Maria Nuria Peralta-Moreno","orcid":"0000-0002-7762-0406","position":5,"is_corresponding":false},{"id":1394238,"name":"Pilar Montanyà-Valluguera","orcid":null,"position":6,"is_corresponding":false},{"id":1394239,"name":"Josep Ponsetí-Pons","orcid":null,"position":7,"is_corresponding":false},{"id":876524,"name":"Montserrat Abella","orcid":"0000-0002-5472-7788","position":8,"is_corresponding":false},{"id":651189,"name":"Sohyoung Kim","orcid":"0000-0002-6140-7918","position":9,"is_corresponding":false},{"id":974263,"name":"Mireia Díaz","orcid":null,"position":10,"is_corresponding":false},{"id":1176998,"name":"Marta Vilaseca","orcid":"0000-0002-1666-1300","position":11,"is_corresponding":false},{"id":876528,"name":"Paloma Pérez","orcid":"0000-0002-7166-2824","position":12,"is_corresponding":false},{"id":631824,"name":"Juan Fernández‐Recio","orcid":"0000-0002-3986-7686","position":13,"is_corresponding":false},{"id":1393694,"name":"J. Rubio","orcid":"0000-0002-5529-2325","position":14,"is_corresponding":false},{"id":628074,"name":"Diego M. Presman","orcid":"0000-0003-4515-8058","position":15,"is_corresponding":false},{"id":579589,"name":"Gordon L. Hager","orcid":"0000-0002-9300-5331","position":16,"is_corresponding":false},{"id":565978,"name":"Pablo Fuentes‐Prior","orcid":"0000-0002-6618-3204","position":17,"is_corresponding":false},{"id":565979,"name":"Eva Estébanez‐Perpiñá","orcid":"0000-0003-2687-5801","position":18,"is_corresponding":false},{"id":876523,"name":"Andrea Alegre‐Martí","orcid":"0000-0001-6646-8798","position":0,"is_corresponding":true}],"reference_count":133,"raw_metadata":null,"created_at":"2026-07-19T02:49:54.058858Z","pmid":"41118578","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":[]}