Prion properties of the Sup35 protein of yeast Pichia methanolica

The Sup35 protein (Sup35p) of Saccharomyces cerevisiae is a translation ter mination factor of the eRF3 family, The proteins of this family possess a c onservative C-terminal domain responsible for translation termination and N -terminal extensions of different structure, The N-terminal domain of Sup35 p defines its ability to undergo a heritable prion-like conformational swit ch, which is manifested as the cytoplasmically inherited [PSI+] determinant . Here, we replaced the N-terminal domain of S. cerevisiae Sup35p with an a nalogous domain from Pichia methanolica. Overexpression of hybrid Sup35p in duced the de novo appearance of cytoplasmically inherited suppressor determ inants manifesting key genetic and biochemical traits of [PSI+], In contras t to the con conventional [PSI+], 'hybrid' [PSI+] showed lower mitotic stab ility and preserved their suppressor phenotype upon overexpression of the H sp104 chaperone protein. The lack of Hsp104 eliminated both types of [PSI+] . No transfer of prion state between the two Sup35p variants was observed, which reveals a 'species barrier' for the [PSI+] prions, The data obtained show that prion properties are conserved within at least a part of this pro tein family.