4.8 Article

Structure of Hsp90-Hsp70-Hop-GR reveals the Hsp90 client-loading mechanism

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Summary: The study reveals the cryo-electron microscopy structure of human GR-maturation complex (GR-Hsp90-p23), showing that the GR ligand-binding domain is restored to folded, ligand-bound conformation and threaded through the Hsp90 lumen, with p23 directly stabilizing native GR through a C-terminal helix, enhancing ligand binding. This client bound to Hsp90 structure contrasts with the unfolded kinase-Hsp90 structure, indicating that Hsp90 can dictate client-specific folding outcomes through direct co-chaperone-client interactions.

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