Extended Data Fig. 9: Hsp70 inhibits GR by binding the pre-Helix 1 region of GR.
From: Structure of Hsp90–Hsp70–Hop–GR reveals the Hsp90 client-loading mechanism
a, After engaging with Hsp70/Hsp40, the GRpre-Helix 1 region exhibits protection from deuterium incorporation in a HD-exchange mass spectrometry (HDX-MS) experiment8. In the GRpre-Helix 1 region, there are Hsp70-binding sites predicted by two state-of-the-art algorithms (BiP Pred58 and ChaperISM59). b, Left, GRLBD crystal structure (PDB ID: 1M2Z) coloured by the change of deuterium uptake (HDX-MS data was retrieved from a previous study)8; green: protection from deuterium incorporation; yellow: positive deuterium uptake. Right, the detachment of the entire GRHelix 1 motif explains the positive deuterium uptake around the ligand-binding pocket. c, The protection from deuterium incorporation of the GRpre-Helix 1 region can be explained by the binding of Hsp70. Together b and c provide a molecular mechanism describing how Hsp70 can inhibit GR ligand binding. d, GR’s pre-Helix 1 remains bound to Hsp70CSBD-β (red circles) in the loading complex. Left, the 6Å low-pass filtered cryo-EM map of the loading complex. Right, atomic model with ribbon presentation.
