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Updated: Jun 27, 2025
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Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models
Published on: November 11, 2014
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Design principles to tailor Hsp104 therapeutics
JiaBei Lin1, Peter J Carman1,2, Craig W Gambogi1,2
1Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104. U.S.A.
Biorxiv : the Preprint Server for Biology
|May 7, 2024
Summary
The AAA+ disaggregase Hsp104
Area of Science:
- Protein aggregation
- Molecular chaperones
- AAA+ disaggregases
Background:
- Hsp104, a hexameric AAA+ disaggregase, works with Hsp70 and Hsp40 to dissolve protein aggregates.
- The precise mechanisms by which ATP- or ADP-bound states of Hsp104's middle domain (MD) control its function are not fully understood.
Conclusions:
- Established that the NBD1:MD helix L1 interface acts as a rheostat to fine-tune Hsp70 collaboration.
- Rational design of this interface allows for safe potentiation of Hsp104, minimizing toxicity.
- Demonstrated therapeutic potential by counteracting FUS proteinopathy in human cells, providing design principles for Hsp104-based therapies.
