Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor.
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:
Dec 2023
Dec 2023
Historique:
received:
10
01
2023
accepted:
18
09
2023
pubmed:
10
11
2023
medline:
10
11
2023
entrez:
9
11
2023
Statut:
ppublish
Résumé
Hsp90 is an essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins, including the glucocorticoid receptor (GR). Previously, we revealed that Hsp70 and Hsp90 remodel the conformation of GR to regulate ligand binding, aided by co-chaperones. In vivo, the co-chaperones FKBP51 and FKBP52 antagonistically regulate GR activity, but a molecular understanding is lacking. Here we present a 3.01 Å cryogenic electron microscopy structure of the human GR:Hsp90:FKBP52 complex, revealing how FKBP52 integrates into the GR chaperone cycle and directly binds to the active client, potentiating GR activity in vitro and in vivo. We also present a 3.23 Å cryogenic electron microscopy structure of the human GR:Hsp90:FKBP51 complex, revealing how FKBP51 competes with FKBP52 for GR:Hsp90 binding and demonstrating how FKBP51 can act as a potent antagonist to FKBP52. Altogether, we demonstrate how FKBP51 and FKBP52 integrate into the GR chaperone cycle to advance GR to the next stage of maturation.
Identifiants
pubmed: 37945740
doi: 10.1038/s41594-023-01128-y
pii: 10.1038/s41594-023-01128-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1867-1877Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
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