Molecular basis of a yeast prion species barrier

The yeast [PSI+] factor is inherited by a prion mechanism involving self-pr opagating Sup35p aggregates. We find that Sup35p prion function is conserve d among distantly related yeasts. As with mammalian prions, a species barri er inhibits prion induction between Sup35p from different yeast species. Th is barrier is faithfully reproduced in vitro where, remarkably, ongoing pol ymerization of one Sup35p species does not affect conversion of another. Ch imeric analysis identifies a short domain sufficient to allow foreign Sup35 p to cross this barrier. These observations argue that the species barrier results from specificity in the growing aggregate, mediated by a well-defin ed epitope on the amyloid surface and, together with our identification of a novel yeast prion domain, show that multiple prion-based heritable states can propagate independently within one cell.