title: Wild yeast harbour a variety of distinct amyloid structures with strong prion-inducing capabilities.
abstract: Variation in amyloid structures profoundly influences a wide array of pathological phenotypes in mammalian protein conformation disorders and dominantly inherited phenotypes in yeast. Here, we describe, for the first time, naturally occurring, self-propagating, structural variants of a prion protein isolated from wild strains of the yeast Saccharomyces cerevisiae. Variants of the [RNQ⁺] prion propagating in a variety of wild yeast differ biochemically, in their intracellular distributions, and in their ability to promote formation of the [PSI⁺] prion. [PSI⁺] is an epigenetic regulator of cellular phenotype and adaptability. Strikingly, we find that most natural [RNQ⁺] variants induced [PSI⁺] at high frequencies and the majority of [PSI⁺] variants elicited strong cellular phenotypes. We hypothesize that the presence of an efficient [RNQ⁺] template primes the cell for [PSI⁺] formation in order to induce [PSI⁺] in conditions where it would be advantageous. These studies utilize naturally occurring structural variants to expand our understanding of the consequences of diverse prion conformations on cellular phenotypes.
authors.affiliation: Department of Cell Biology and Physiology, Washington University, St Louis, MO, 63110, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Westergard
authors.forename: Heather L
authors.initials: HL
authors.lastname: True
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D010454:Peptide Termination Factors / Q000378:metabolism*; D010641:Phenotype; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D013696:Temperature
chemical_list: D010454:Peptide Termination Factors; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins