| Autor: |
Eva Estébanez-Perpiñá, Paloma Pérez, Juan Fernández-Recio, Theophilus Tettey, Montserrat Abella, Israel Nuñez-Barrios, Joan Font-Díaz, Pablo Fuentes-Prior, Andrea Alegre-Martí, Thomas A. Johnson, Annabel F. Valledor, Grégory Fettweis, Ana M. Rojas, Rosa Antón, Louis Schiltz, Gordon L. Hager, Diego M. Presman, Carme Caelles, Alba Jiménez-Panizo |
| Rok vydání: |
2021 |
| Předmět: |
|
| DOI: |
10.1101/2021.10.01.462734 |
| Popis: |
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. Biologically relevant homodimers were identified by studying a battery of GR point mutants including crosslinking assays in solution and quantitative fluorescence microscopy in living cells. 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 unveils likely pathophysiologically relevant quaternary assemblies of the nuclear receptor with important implications for glucocorticoid action and drug design. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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