Extended conformational states dominate the Hsp90 chaperone dynamics
Alexander Jussupow1, Abraham Lopez2, Mona Baumgart3
1Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
The Journal of Biological Chemistry
|June 6, 2022
Summary
Heat shock protein 90 (Hsp90) conformational dynamics are key to its function. Molecular simulations reveal how a charged linker and β-sheet motif control Hsp90
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Heat shock protein 90 (Hsp90) is a crucial molecular chaperone.
- Hsp90 regulates client protein folding and maturation in eukaryotic cells.
- Hsp90's function involves large conformational changes between open and closed states.
Purpose of the Study:
- To elucidate the molecular mechanisms governing Hsp90's conformational switching.
- To understand the role of specific protein regions in Hsp90 dynamics.
Main Methods:
- Atomistic and coarse-grained molecular simulations.
- Small-angle X-ray scattering (SAXS) experiments.
- Nuclear Magnetic Resonance (NMR) spectroscopy.
Main Results:
- Hsp90 exhibits diverse conformational dynamics influenced by its charged linker.
- Dissociation of N-terminal and middle domains is vital for the open state's flexibility.
- A β-sheet motif adjacent to the linker regulates domain separation distance.
Conclusions:
- Hsp90's conformational ensemble includes highly extended states.
- These extended conformations are likely critical for Hsp90's client processing function.
- The charged linker and associated structural elements are key regulators of Hsp90 conformational flexibility.
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