Extended Data Fig. 5: Both the Hsp90^ATP and the Hsp70^ATP conformations are incompatible with the GR-loading complex.

a, Overlay of the crystal structure of Apo Hsp90 fragment (purple; PDB ID: 3T0H⁵⁴) to the Hsp90A_NTD (dark blue). Green circle highlights the open ATP pocket lid. b, Closure of the ATP pocket lid in the ATP state of Hsp90_NTD (the Hsp90α structure from the GR-maturation complex⁹ is in yellow, ribbon representation) clashes (magenta circle) with the Hsp70_NBD (orange, surface and ribbon representation) in the loading complex. The NTD fragment of Hsp90^ATP is aligned with the Hsp90_NTD in the loading complex. c, Superimposition of the ATP state of Hsp90_NTD-MD fragment (yellow) to the Hsp90A (dark blue) at the MD. Magenta circles indicate steric clashes of the ATP state of the Hsp90_NTD to the Hsp70_NBD (orange; surface/ribbon representation). d, Superposition of the Hsp70^ATP conformation (green; PDB ID: 4B9Q⁷⁵) to the Hsp70C_NBD (dark orange). Arrows indicate the two subdomains of Hsp70^ATP_SBD, which cause serious steric clashes with the Hsp90 in the loading complex shown in e. e, The superimposed Hsp70^ATP shown in e is fixed from d and the Hsp90 (dark blue; surface/ribbon representation) of the GR-loading complex is present. Magenta circles highlight steric clashes caused by the two subdomains of Hsp70^ATP_SBD (green) to the Hsp90A_NTD-MD.