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Strains of [ PSI + ] are distinguished by their efficiencies of prion‐mediated conformational conversion
Author(s) -
Uptain Susan M.,
Sawicki George J.,
Caughey Byron,
Lindquist Susan
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.22.6236
Subject(s) - prion protein , yeast , strain (injury) , phenotype , fungal prion , saccharomyces cerevisiae , chemistry , in vitro , translation (biology) , biology , genetics , biophysics , microbiology and biotechnology , gene , messenger rna , disease , medicine , pathology , anatomy
Yeast prions are protein‐based genetic elements that produce phenotypes through self‐perpetuating changes in protein conformation. For the prion [ PSI + ] this protein is Sup35, which is comprised of a prion‐determining region (NM) fused to a translational termination region. [ PSI + ] strains (variants) with different heritable translational termination defects (weak or strong) can exist in the same genetic background. [ PSI + ] variants are reminiscent of mammalian prion strains, which can be passaged in the same mouse strain yet have different disease latencies and brain pathologies. We found that [ PSI + ] variants contain different ratios of Sup35 in the prion and non‐prion state that correlate with different translation termination efficiencies. Indeed, the partially purified prion form of Sup35 from a strong [ PSI + ] variant converted purified NM much more efficiently than that of several weak variants. However, this difference was lost in a second round of conversion in vitro . Thus, [ PSI + ] variants result from differences in the efficiency of prion‐mediated conversion, and the maintenance of [ PSI + ] variants involves more than nucleated conformational conversion (templating) to NM alone.