Extended Data Fig. 4: Hsp90:FKBP52 Interfaces in the GR:Hsp90:FKBP52 Complex.
From: Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor
Atomic model of the GR:Hsp90:FKBP52 complex with Hsp90A (dark blue), Hsp90B (light blue), GR (yellow), and FKBP52 (teal). Side chains in contact between Hsp90 and FKBP52 are shown, along with hydrogen bonds (dashed pink lines). a, Interface 1 of the Hsp90:FKBP52 interaction depicting the FKBP52 TPR H7e binding to the Hsp90A/B CTD dimer interface. The helix of FKBP52 H7e breaks to fit into the cleft formed by the Hsp90 CTDs. b, Interface 2 of the Hsp90:FKBP52 interaction depicting the Hsp90B MEEVD motif binding the FKBP52 TPR helical bundle. c, Interface 3 of the Hsp90:FKBP52 interaction depicting the FKBP52 TPR Helices 5 and 6 binding to the Hsp90B CTD. d, FKBP52 (teal) from the GR:Hsp90:FKBP52 atomic model aligned with the cryo-EM structure of FKBP51 (light blue) (PDB ID 7L7I) (top) and crystal structures of FKBP52 (PDB ID 1P5Q, 1Q1C) (bottom) showing the difference in interdomain angles. 1P5Q contains the FKBP52 FK1 and FK2 domain, while 1Q1C contains the FKBP52 FK2 and TPR domains. e, The GR:Hsp90:FKBP52 atomic model with FKBP52 (teal), GR (yellow), and dexamethasone (pink) with proline-isomerase inhibitors, rapamycin (brown) or FK506 (orange), docked into the atomic model to indicate the steric clash with GR. Rapamycin was docked in based on the FKBP52:rapamycin crystal structure (PDB ID 4DRJ) and FK506 was docked in based on the FKBP52:FK506:FRB crystal structure (PDB ID 4LAX).
