Evidence for the prion hypothesis: Induction of the yeast [PSI+] factor byin vitro-converted Sup35 protein

Starting with purified, bacterially produced protein, we have created a [PS I+]-inducing agent based on an altered (prion) conformation of the yeast Su p35 protein. After converting Sup35p to its prion conformation in vitro, we introduced it into the cytoplasm of living yeast using a liposome transfor mation protocol. Introduction of substoichiometric quantities of converted Sup35p greatly increased the rate of appearance of the well-characterized e pigenetic factor [PSI+], which results from self-propagating aggregates of cellular Sup35p. Thus, as predicted by the prion hypothesis, proteins can a ct as infectious agents by causing self-propagating conformational changes.