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Updated: May 25, 2026
06:51
Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay
Published on: July 21, 2021
Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity
Shinji Tsutsumi1, Mehdi Mollapour, Chrisostomos Prodromou
1Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Summary
The charged linker in heat shock protein 90 (Hsp90) is crucial for its function, influencing cochaperone interactions and conformation. This evolutionary feature acts as a rheostat, fine-tuning the Hsp90 chaperone machine.
Area of Science:
- Molecular biology
- Biochemistry
- Evolutionary biology
Background:
- Heat shock protein 90 (Hsp90) is a vital molecular chaperone conserved across eukaryotes.
- The charged linker region separating Hsp90 domains has been considered non-essential due to minimal length requirements for activity.
- The evolutionary persistence of long, divergent charged linkers in Hsp90 remains poorly understood.
Purpose of the Study:
- To investigate the functional significance of the Hsp90 charged linker sequence.
- To determine how native and artificial linkers impact Hsp90 ATPase activity, biophysical properties, and chaperone function.
- To explore the role of the charged linker in Hsp90 conformational dynamics and cochaperone interactions.
Main Methods:
- Introduction of human and Plasmodium native and length-matched artificial linkers into yeast Hsp90.
- In vitro assessment of ATPase activity and biophysical characteristics.
- In vivo evaluation of Hsp90 chaperone function.
Main Results:
- Linker sequence significantly affects Hsp90 ATPase activity and biophysical properties.
- Variations in linker sequence alter Hsp90's ability to perform its chaperone function in vivo.
- The charged linker influences interactions with Hsp90 cochaperones and affects overall protein conformation.
Conclusions:
- The Hsp90 charged linker is not merely a flexible spacer but actively modulates chaperone activity.
- Linker sequence serves as a regulatory element, akin to a rheostat, controlling the Hsp90 chaperone machine.
- Evolution has refined the charged linker to play a critical role in eukaryotic Hsp90 function beyond basic domain flexibility.
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