2026-04-13T02:28:35Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2281842026-04-07T19:02:55Zcom_2072_1057col_2072_478781col_2072_478917

urn:hdl:2445/228184 The multimerization pathway of the glucocorticoid receptor Biologia molecular Molecular biology 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. 2026-03-17T13:41:11Z 2026-03-17T13:41:11Z 2025-10-21 2026-03-17T13:41:12Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1093/nar/gkaf1003 Nucleic Acids Research, 2025, vol. 53, num.19, p. 1-24 https://doi.org/10.1093/nar/gkaf1003 cc-by-nc (c) Alegre-Marti, A. et al., 2025 http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess Oxford University Press Articles publicats en revistes (Bioquímica i Biomedicina Molecular)