title: Soluble oligomers are sufficient for transmission of a yeast prion but do not confer phenotype.
abstract: Amyloidogenic proteins aggregate through a self-templating mechanism that likely involves oligomeric or prefibrillar intermediates. For disease-associated amyloidogenic proteins, such intermediates have been suggested to be the primary cause of cellular toxicity. However, isolation and characterization of these oligomeric intermediates has proven difficult, sparking controversy over their biological relevance in disease pathology. Here, we describe an oligomeric species of a yeast prion protein in cells that is sufficient for prion transmission and infectivity. These oligomers differ from the classic prion aggregates in that they are soluble and less resistant to SDS. We found that large, SDS-resistant aggregates were required for the prion phenotype but that soluble, more SDS-sensitive oligomers contained all the information necessary to transmit the prion conformation. Thus, we identified distinct functional requirements of two types of prion species for this endogenous epigenetic element. Furthermore, the nontoxic, self-replicating amyloid conformers of yeast prion proteins have again provided valuable insight into the mechanisms of amyloid formation and propagation in cells.
authors.affiliation: Department of Cell Biology and Physiology, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Dulle
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Bouttenot
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Underwood
authors.forename: Heather L
authors.initials: HL
authors.lastname: True
mesh_terms: D044127:Epigenesis, Genetic; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010454:Peptide Termination Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D013997:Time Factors
chemical_list: D006360:Heat-Shock Proteins; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae