Quaternary glucocorticoid receptor structure highlights allosteric interdomain communication.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
05
04
2022
accepted:
15
12
2022
pubmed:
8
2
2023
medline:
22
3
2023
entrez:
7
2
2023
Statut:
ppublish
Résumé
The glucocorticoid receptor (GR) is a ligand-activated transcription factor that binds DNA and assembles co-regulator complexes to regulate gene transcription. GR agonists are widely prescribed to people with inflammatory and autoimmune diseases. Here we present high-resolution, multidomain structures of GR in complex with ligand, DNA and co-regulator peptide. The structures reveal how the receptor forms an asymmetric dimer on the DNA and provide a detailed view of the domain interactions within and across the two monomers. Hydrogen-deuterium exchange and DNA-binding experiments demonstrate that ligand-dependent structural changes are communicated across the different domains in the full-length receptor. This study demonstrates how GR forms a distinct architecture on DNA and how signal transmission can be modulated by the ligand pharmacophore, provides a platform to build a new level of understanding of how receptor modifications can drive disease progression and offers key insight for future drug design.
Identifiants
pubmed: 36747092
doi: 10.1038/s41594-022-00914-4
pii: 10.1038/s41594-022-00914-4
doi:
Substances chimiques
Receptors, Glucocorticoid
0
Ligands
0
Transcription Factors
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
286-295Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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