Extended Data Fig. 3: The Hsp90 in both two-Hsp70 and one-Hsp70 GR-loading complexes adopts a semi-closed conformation.
From: Structure of Hsp90–Hsp70–Hop–GR reveals the Hsp90 client-loading mechanism
a, Close-up view of the novel dimerization interface of the symmetric Hsp90 dimer with residues at the interface in transparent surface representation. The interface is composed of two molecular switches of Hsp90, the first helix and the lid motif. b, c, The Hsp90 in the loading complex (b) is one step away from the fully closed ATP state (c). Front (left) and side (right) views of the Hsp90 in the two-Hsp90 GR-loading complex (b) and the Hsp90 in the GR-maturation complex9 (c). Arrows indicate displacements from the Hsp90 in the loading state, in which a large twisting motion is apparent from the side view. d, Comparison of cryo-EM reconstructions of the one-Hsp70 and two-Hsp70 GR-loading complexes. Schematic model of the two-Hsp70 loading complex (left). Front views of cryo-EM maps of the two-Hsp70 (middle; grey colour) and one-Hsp70 (right; salmon colour) GR-loading complexes. Right, the one-Hsp70 reconstruction has lost density for Hsp70CNBD (dashed circle) and Hsp70CSBD-α (red arrows); however, density for GRpre-Helix 1 and GRHelix 1 (black arrows) is in the same location as it is in the two-Hsp70 GR-loading complex. e, Rigid-body fitting of the two Hsp90 protomers individually in the one- or two-Hsp70 loading complexes cryo-EM reconstructions shows both of the Hsp90s share a similar semi-closed conformation. The Hsp90 in the one-Hsp70 loading complex (middle panel) has a slightly wider opening angle (right panel) than the Hsp90 in the two-Hsp70 loading complex (left panel). f, The lumen of the semi-closed Hsp90 presented in the loading complex can fit a helix72. A helix (magenta) can be accommodated in the semi-closed Hsp90. Front view (left) and top view (right).
