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Hsp70/Hsp90 co‐chaperones are required for efficient Hsp104‐mediated elimination of the yeast [ PSI + ] prion but not for prion propagation
Author(s) -
Moosavi Behrooz,
Wongwigkarn Jintana,
Tuite Mick F.
Publication year - 2010
Publication title -
yeast
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 102
eISSN - 1097-0061
pISSN - 0749-503X
DOI - 10.1002/yea.1742
Subject(s) - chaperone (clinical) , mutant , biology , saccharomyces cerevisiae , microbiology and biotechnology , yeast , biochemistry , protein aggregation , plasma protein binding , hsp90 , gene , heat shock protein , medicine , pathology
The continued propagation of the yeast [ PSI + ] prion requires the molecular chaperone Hsp104 yet in cells engineered to overexpress Hsp104; prion propagation is impaired leading to the rapid appearance of prion‐free [ psi − ] cells. The underlying mechanism of prion loss in such cells is unknown but is assumed to be due to the complete dissolution of the prion aggregates by the ATP‐dependent disaggregase activity of this chaperone. To further explore the mechanism, we have sought to identify cellular factors required for prion loss in such cells. Sti1p and Cpr7p are co‐chaperones that modulate the activity of Hsp70/Ssa and Hsp90 chaperones and bind to the C‐terminus of Hsp104. Neither Sti1p nor Cpr7p is necessary for prion propagation but we show that deletion of the STI1 and CPR7 genes leads to a significant reduction in the generation of [ psi − ] cells by Hsp104 overexpression. Deletion of the STI1 and CPR7 genes does not modify the elimination of [ PSI + ] by guanidine hydrochloride, which inhibits the ATPase activity of Hsp104 but does block elimination of [ PSI + ] by overexpression of either an ATPase‐defective mutant of Hsp104 ( hsp104 K218T/K620T ) or a ‘trap’ mutant Hsp104 ( hsp104 E285Q/E687Q ) that can bind its substrate but can not release it. These results provide support for the hypothesis that [ PSI + ] elimination by Hsp104 overexpression is not simply a consequence of complete dissolution of the prion aggregates but rather is through a mechanism distinct from the remodelling activity of Hsp104. Copyright © 2009 John Wiley & Sons, Ltd.