Extended Data Fig. 3: Hsp90:GR Interfaces in the GR:Hsp90:FKBP52 Complex.
From: Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor
a, Hsp90:GR:FKBP52 complex map density with atomic model showing ATP-magnesium density in both Hsp90 protomers (Hsp90A/B). Bottom images show increased contour level on the map density to indicate that the ATP γ-phosphate position has much stronger density relative to the α and β-phosphates, likely corresponding to molybdate, which may act as a γ-phosphate analog (see Methods). b, Atomic model of GR from the GR:Hsp90:FKBP52 complex (yellow) aligned with GR from the crystal structure (PDB ID 1M2Z) (light pink) with co-activator peptide NCoA2 (purple) and GR from the GR-maturation complex structure (PDB ID 7KRJ). GR Helix 12 is indicated. c-f, Atomic model of GR:Hsp90:FKBP52 complex with Hsp90A (dark blue), Hsp90B (light blue), GR (yellow). Side chains in contact between GR and Hsp90 are shown, along with hydrogen bonds (dashed pink lines).c, Interface 1 of the GR:Hsp90 interaction depicting the GR hydrophobic patch (GR Helices 9 and 10) interacting with the Hsp90A Src loop (Hsp90345–360), Hsp90AW320, and Hsp90A NTD/MD helices. d, Interface 2 of the GR:Hsp90 interaction depicting the GR pre-Helix 1 strand and Helix 1 packing up against the Hsp90B amphipathic α-helices. e, Interface 2 of the GR:Hsp90 interaction depicting GR in surface representation colored by hydrophobicity (green = polar, brown = nonpolar) with Hsp90BY627 sticking into the BF3 druggable hydrophobic pocket. f, Interface 3 of the GR:Hsp90 interaction depicting the GR pre-Helix 1 strand threading through the Hsp90 lumen between Hsp90A and Hsp90B.
