Supporting the structural basis of prion strains: induction and identification of [PSI] variants

J Mol Biol. 2001 Apr 13;307(5):1247-60. doi: 10.1006/jmbi.2001.4542.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism*
  • Genes, Dominant / genetics
  • Genetic Variation / genetics*
  • Peptide Termination Factors
  • Phenotype
  • Point Mutation / genetics
  • Prions / chemistry
  • Prions / genetics*
  • Prions / metabolism*
  • Protein Conformation
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Suppression, Genetic / genetics*


  • Fungal Proteins
  • Peptide Termination Factors
  • Prions
  • Recombinant Fusion Proteins
  • SUP35 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins