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The Mechanism of [PSI+] Prion Curing in Response to Mild Thermal Stress
Author(s) -
Klaips Courtney Lee,
Serio Tricia R
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.954.7
Subject(s) - chaperone (clinical) , protein aggregation , hsp70 , microbiology and biotechnology , heat shock protein , yeast , biophysics , chemistry , phenotype , protein folding , in vivo , biology , biochemistry , genetics , medicine , pathology , gene
Prions are proteins that can adopt more than one stable conformation in vivo . Remarkably, the alternative non‐native conformers can self‐replicate their folds by forming aggregates that template the conversion of native conformers to a like state. Because these conformational changes alter the normal activity of the protein, the self‐replication process allows prions to confer new and transmissible phenotypes. In yeast, the fragmentation of prion aggregates by the molecular disaggregase Hsp104, along with its Hsp70 and Hsp40 co‐chaperones, to create new templates and to facilitate their partitioning to daughter cells is an essential step in this pathway. But the expression and activities of these and other factors mediating protein quality control are profoundly altered by external stresses. While such changes in environmental conditions have been reported to “cure” certain variants of the [ PSI + ]/Sup35 prion in yeast, the mechanisms by which these transitions occur are poorly understood. Here, we report that mild heat shock cures [ PSI + ] by dissolving existing prion aggregates. Our studies suggest that these effects are mediated not simply by the increase in chaperone expression but rather by the interplay between ordered, prion aggregates, and disordered, heat‐induced protein aggregates in the engagement of these factors. This work is supported by NIH grant F31AGO34754.