Prion variant maintained only at high levels of the Hsp104 disaggregase.
The yeast prion [PSI(+)] is a self-perpetuating aggregated isoform of the translation termination factor Sup35. [PSI ( + )] propagation is promoted by moderate levels and antagonized by high levels of the chaperone Hsp104. In agreement with the model postulating that excess Hsp104 acts on [PSI ( + )] by disaggregating prion polymers, we show that an increase in Sup35 levels, accompanied by an increase in size of prion aggregates, also partially protects [PSI(+)] from elimination by excess Hsp104. Despite retention of [PSI(+)], excess Hsp104 decreases toxicity of overproduced Sup35 in [PSI(+)] strains. A heritable variant of [PSI(+)], which has been isolated and is maintained only in the presence of increased levels of Hsp104, is characterized by an abnormally large aggregate size, and exhibits an altered response to overproduction of the Hsp70 chaperone Ssa1. These features resemble the previously described prion generated by a deletion derivative of Sup35, but are not associated with any sequence alteration and are controlled exclusively at the protein level. Our data provide a proof of the existence of conditionally stable prion variants maintained only at altered levels of Hsps, that could in principle be beneficial if the normal cellular function of a prion protein becomes detrimental to the cell in such conditions.
Borchsenius
Andrey S
AS
School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, 30332-0230, USA.
Müller
Susanne
S
Newnam
Gary P
GP
Inge-Vechtomov
Sergey G
SG
Chernoff
Yury O
YO
D006360:Heat-Shock Proteins / Q000378:metabolism*; D018832:Molecular Chaperones; D010454:Peptide Termination Factors; D011328:Prions / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae