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Updated: Jul 28, 2026
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Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Control of estrogen receptor ligand binding by Hsp90
1Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, NY 10029, New York, USA.
Summary
The molecular chaperone heat shock protein 90 (Hsp90) is crucial for maintaining the estrogen receptor (ER) in a conformation that binds hormones effectively. Disrupting Hsp90 function impairs estrogen receptor hormone binding.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- The molecular chaperone heat shock protein 90 (Hsp90) plays a key role in the function of steroid hormone receptors.
- Hsp90 is known to interact with unliganded steroid hormone receptors, regulating their activity.
Purpose of the Study:
- To investigate the function of yeast and mammalian Hsp90 in regulating the ligand-binding ability of the human estrogen receptor (ER).
- To determine if Hsp90 maintains the ER in a high-affinity hormone-binding conformation.
Main Methods:
- Utilized a yeast system to express the human ER in hsp82 mutant strains and wild-type strains.
- Analyzed ER protein levels and binding of the synthetic estrogen diethylstilbestrol (DES).
- Synthesized the human ER in rabbit reticulocyte lysates with varying concentrations of geldanamycin, an Hsp90 inhibitor.
Main Results:
- ER expressed in hsp82 mutant yeast strains showed reduced binding of diethylstilbestrol without significant changes in ER protein levels.
- In vitro studies using geldanamycin showed reduced ER hormone binding at low inhibitor concentrations.
- Higher concentrations of geldanamycin led to reduced synthesis of the ER protein.
Conclusions:
- Hsp90 is essential for maintaining the human estrogen receptor in a conformation that allows for high-affinity hormone binding.
- Hsp90 influences both the ligand-binding capacity and the synthesis of the estrogen receptor.
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