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Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay
Published on: July 21, 2021
The chaperone Hsp90: changing partners for demanding clients
Alina Röhl1, Julia Rohrberg, Johannes Buchner
1Center for Integrated Protein Science (CIPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
Trends in Biochemical Sciences
|March 20, 2013
Summary
Heat shock protein 90 (Hsp90) machinery uses co-chaperones to regulate client proteins. These co-chaperones stabilize intermediate states, guiding Hsp90
Area of Science:
- Molecular Biology
- Protein Folding and Chaperones
- Cellular Regulation
Background:
- Heat shock protein 90 (Hsp90) is a crucial molecular chaperone regulating hundreds of client proteins in the eukaryotic cytosol.
- Hsp90 functions through an ATPase cycle involving large, energetically similar conformational changes.
- Co-chaperones are known to influence Hsp90's conformational states and ATPase activity.
Purpose of the Study:
- To elucidate the role of Hsp90 co-chaperones in modulating the chaperone's conformational equilibrium.
- To understand the ordered progression of co-chaperones during the Hsp90 conformational cycle.
- To investigate the potential significance of asymmetric co-chaperone complexes in client protein processing.
Main Methods:
- Analysis of Hsp90 conformational dynamics.
- Characterization of Hsp90-co-chaperone interactions.
- Investigating client protein interactions with the Hsp90 machinery.
Main Results:
- Hsp90 co-chaperones stabilize specific intermediate conformational states.
- A sequential order of co-chaperone binding occurs during the Hsp90 conformational cycle.
- Asymmetric Hsp90-co-chaperone complexes may play a role in client protein maturation.
Conclusions:
- Co-chaperones are critical regulators of Hsp90 conformational states and ATPase activity.
- The ordered recruitment of co-chaperones dictates the progression through the Hsp90 cycle.
- Further research is needed to fully understand Hsp90-client and asymmetric co-chaperone interactions.
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