9HDF
Glucocorticoid Receptor Ligand Binding Domain in complex with dexamethasone
Summary for 9HDF
| Entry DOI | 10.2210/pdb9hdf/pdb |
| Descriptor | Ancestral Glucocorticoid Receptor2 ligand binding domain, TETRAETHYLENE GLYCOL, IMIDAZOLE, ... (14 entities in total) |
| Functional Keywords | nuclear receptor, glucocorticoid receptor, dna binding protein |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 32 |
| Total formula weight | 497634.54 |
| Authors | Alegre-Marti, A.,Jimenez-Panizo, A.,Fuentes-Prior, P.,Estebanez-Perpina, E. (deposition date: 2024-11-12, release date: 2025-11-12) |
| Primary citation | Alegre-Marti, A.,Jimenez-Panizo, A.,Lafuente, A.L.,Johnson, T.A.,Montoya-Novoa, I.,Peralta-Moreno, M.N.,Montanya-Valluguera, P.,Ponseti-Pons, J.,Abella, M.,Kim, S.,Diaz, M.,Vilaseca, M.,Perez, P.,Fernandez-Recio, J.,Rubio-Martinez, J.,Presman, D.M.,Hager, G.L.,Fuentes-Prior, P.,Estebanez-Perpina, E. The multimerization pathway of the glucocorticoid receptor. Nucleic Acids Res., 53:-, 2025 Cited by PubMed 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. PubMed: 41118578DOI: 10.1093/nar/gkaf1003 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.78 Å) |
Structure validation
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