7YXR
Crystal structure of mutant AncGR2-LBD (Y545A) bound to dexamethasone and SHP coregulator fragment
Summary for 7YXR
| Entry DOI | 10.2210/pdb7yxr/pdb |
| Descriptor | Ancestral Glucocorticoid Receptor2, SHP NR Box 1 Peptide, DEXAMETHASONE, ... (5 entities in total) |
| Functional Keywords | nuclear receptor, transcription factor, dexamethasone, mutant, nuclear protein |
| Biological source | unidentified More |
| Total number of polymer chains | 4 |
| Total formula weight | 60878.79 |
| Authors | Jimenez-Panizo, A.,Estebanez-Perpina, E.,Fuentes-Prior, P. (deposition date: 2022-02-16, release date: 2022-12-07, Last modification date: 2024-01-31) |
| Primary citation | Jimenez-Panizo, A.,Alegre-Marti, A.,Tettey, T.T.,Fettweis, G.,Abella, M.,Anton, R.,Johnson, T.A.,Kim, S.,Schiltz, R.L.,Nunez-Barrios, I.,Font-Diaz, J.,Caelles, C.,Valledor, A.F.,Perez, P.,Rojas, A.M.,Fernandez-Recio, J.,Presman, D.M.,Hager, G.L.,Fuentes-Prior, P.,Estebanez-Perpina, E. The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities. Nucleic Acids Res., 50:13063-13082, 2022 Cited by PubMed Abstract: The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. Although numerous crystal structures of the GR ligand-binding domain (GR-LBD) have been reported, the functional oligomeric state of the full-length receptor, which is essential for its transcriptional activity, remains disputed. Here we present five new crystal structures of agonist-bound GR-LBD, along with a thorough analysis of previous structural work. We identify four distinct homodimerization interfaces on the GR-LBD surface, which can associate into 20 topologically different homodimers. Biologically relevant homodimers were identified by studying a battery of GR point mutants including crosslinking assays in solution, quantitative fluorescence microscopy in living cells, and transcriptomic analyses. Our results highlight the relevance of non-canonical dimerization modes for GR, especially of contacts made by loop L1-3 residues such as Tyr545. Our work illustrates the unique flexibility of GR's LBD and suggests different dimeric conformations within cells. In addition, we unveil pathophysiologically relevant quaternary assemblies of the receptor with important implications for glucocorticoid action and drug design. PubMed: 36464162DOI: 10.1093/nar/gkac1119 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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