title: Supporting the structural basis of prion strains: induction and identification of [PSI] variants.
abstract: The [PSI] genetic element, which enhances the nonsense suppression efficiency in the yeast Saccharomyces cerevisiae, is thought to be amyloid-like aggregates of the Sup35 protein, and to self-propagate by a prion-like mechanism. Analogous to strains of the mammalian prion, variants of [PSI], with different nonsense suppression efficiencies and mitotic stabilities, can be isolated from the same yeast genetic background. In the framework of the "protein-only" hypothesis, variants of prion are assumed to be distinct conformers of the same prion polypeptide. This study aims to provide further support for the structural basis of [PSI] variation. Three variants of [PSI] were induced and distinguished by a panel of 11 single point mutations of the Sup35 protein. The variant phenotypes are intrinsically associated with [PSI] elements, presumably structurally different amyloids, rather than produced from variations in the genetic background. Differential incorporation to [PSI] variants of a Sup35 point mutation as well as N and C-terminally truncated Sup35 fragments is further demonstrated in vivo, suggesting that distinct patches of amino acid residues are involved in the assembly of [PSI] variants. These results establish a method for [PSI] variant-typing and indicate that heritable variations of amyloid structures can be derived from the same polypeptide.
authors: Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, 32306, USA. chihyen@sb.fsu.edu
authors: C Y
authors: CY
authors: King
mesh_terms: D000483:Alleles; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005799:Genes, Dominant / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D010454:Peptide Termination Factors; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; D010454:Peptide Termination Factors; D011328:Prions; D011993:Recombinant Fusion Proteins; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins