Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the Glucocorticoid Receptor.

ABSTRACT: Hsp90 is an essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins, including the glucocorticoid receptor (GR)^1-3. Previously, we revealed that GR ligand binding activity is inhibited by Hsp70 and restored by Hsp90, aided by co-chaperones⁴. We then presented cryo-EM structures mechanistically detailing how Hsp70 and Hsp90 remodel the conformation of GR to regulate ligand binding^5,6. In vivo, GR-chaperone complexes are found associated with numerous Hsp90 co-chaperones, but the most enigmatic have been the immunophilins FKBP51 and FKBP52, which further regulate the activity of GR and other steroid receptors^7-9. A molecular understanding of how FKBP51 and FKBP52 integrate with the GR chapero

SUBMITTER: Noddings CM 

PROVIDER: S-EPMC9882067 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature