title: Extracellular environment modulates the formation and propagation of particular amyloid structures.
abstract: Amyloidogenic proteins, including prions, assemble into multiple forms of structurally distinct fibres. The [PSI(+)] prion, endogenous to the yeast Saccharomyces cerevisiae, is a dominantly inherited, epigenetic modifier of phenotypes. [PSI(+)] formation relies on the coexistence of another prion, [RNQ(+)]. Here, in order to better define the role of amyloid diversity on cellular phenotypes, we investigated how physiological and environmental changes impact the generation and propagation of diverse protein conformations from a single polypeptide. Utilizing the yeast model system, we defined extracellular factors that influence the formation of a spectrum of alternative self-propagating amyloid structures of the Sup35 protein, called [PSI(+)] variants. Strikingly, exposure to specific stressful environments dramatically altered the variants of [PSI(+)] that formed de novo. Additionally, we found that stress also influenced the association between the [PSI(+)] and [RNQ(+)] prions in a way that it superceded their typical relationship. Furthermore, changing the growth environment modified both the biochemical properties and [PSI(+)]-inducing capabilities of the [RNQ(+)] template. These data suggest that the cellular environment contributes to both the generation and the selective propagation of specific amyloid structures, providing insight into a key feature that impacts phenotypic diversity in yeast and the cross-species transmission barriers characteristic of prion diseases.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Westergard
authors.forename: Heather L
authors.initials: HL
authors.lastname: True
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D010454:Peptide Termination Factors / Q000378:metabolism*; D011328:Prions / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D000682:Amyloid; D010454:Peptide Termination Factors; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins