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Updated: Jul 6, 2026

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Studies with Purified Chaperones Advance the Understanding of the Mechanism of Glucocorticoid Receptor-hsp90
1Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Abstract:
The study of the 9S, untransformed state of steroid receptors has led to the discovery of a multiprotein chaperone system that assembles heterocomplexes between hsp90 and a variety of proteins involved in signal transduction. Using the formation of glucocorticoid receptor (GR)-hsp90 heterocomplexes as a model, we have reconstituted a fully functional heterocomplex assembly system from purified components. The basic assembly system requires four proteins-hsp90, hsp70, p60/Hop and hsp40-to assemble GR-hsp90 heterocomplexes, which are then stabilized by the hsp90-interacting protein p23. The four proteins can self-assemble into an hsp90-p60/Hop-hsp70-hsp40 complex that we call a foldosome. Foldosomes isolated from reticulocyte lysate or formed from purified proteins open up a steroid-binding pocket to create a high-affinity steroid-binding state of the GR. We describe here the systematic reconstitution of the hsp90-based chaperone machinery and develop a model of the receptor-hsp90 heterocomplex assembly mechanism.
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