Washington University in St. Louis

New Publication for the True Lab

Congratulations to Kate Keefer and Heather True on their recent publication in Molecular Microbiology!

Kathryn M. Keefer, Heather L. True  (2017) A toxic imbalance of Hsp70s in Saccharomyces cerevisiae is caused by competition for cofactors.  Molecular Microbiology  [E-published online June 30]

Abstract:  Molecular chaperones are responsible for managing protein folding from translation through degradation. These crucial machines ensure that protein homeostasis is optimally maintained for cell health. However, "too much of a good thing" can be deadly, and the excess of chaperones can be toxic under certain cellular conditions. For example, overexpression of Ssa1, a yeast Hsp70, is toxic to cells in folding-challenged states such as [PSI+]. We discovered that overexpression of the nucleotide exchange factor Sse1 can partially alleviate this toxicity. We further argue that the basis of the toxicity is related to the availability of Hsp70 cofactors, such as Hsp40 J-proteins and nucleotide exchange factors. Ultimately, our work informs future studies about functional chaperone balance and cautions against therapeutic chaperone modifications without a thorough examination of cofactor relationships.

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