Strains of [PSI+] are distinguished by their efficiencies of prion-mediated conformational conversion

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.