Prion and nonprion amyloids: a comparison inspired by the yeast Sup35 protein

Prion. 2007 Jul-Sep;1(3):179-84. doi: 10.4161/pri.1.3.4840. Epub 2007 Jul 6.

Abstract

Yeast prion determinants are related to polymerization of some proteins into amyloid-like fibers. The [PSI(+)] determinant reflects polymerization of the Sup35 protein. Fragmentation of prion polymers by the Hsp104 chaperone represents a key step of the prion replication cycle. The frequency of fragmentation varies depending on the structure of the prion polymers and defines variation in the prion phenotypes, e.g., the suppressor strength of [PSI(+)] and stability of its inheritance. Besides [PSI(+)], overproduction of Sup35 can produce nonheritable phenotypically silent Sup35 amyloid-like polymers. These polymers are fragmented poorly and are present due to efficient seeding with the Rnq1 prion polymers, which occurs by several orders of magnitude more frequently than seeding of [PSI(+)] appearance. Such Sup35 polymers resemble human nonprion amyloids by their nonheritability, mode of appearance and increased size. Thus, a single protein, Sup35, can model both prion and nonprion amyloids. In yeast, these phenomena are distinguished by the frequency of polymer fragmentation. We argue that in mammals the fragmentation frequency also represents a key factor defining differing properties of prion and nonprion amyloids, including infectivity. By analogy with the Rnq1 seeding of nonheritable Sup35 polymers, the "species barrier" in prion transmission may be due to seeding by heterologous prion of nontransmissible type of amyloid, rather than due to the lack of seeding.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid / chemistry
  • Amyloid / genetics
  • Amyloid / metabolism*
  • Heat-Shock Proteins / chemistry
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Peptide Termination Factors
  • Prions / chemistry
  • Prions / genetics
  • Prions / metabolism*
  • Protein Structure, Quaternary
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Amyloid
  • Heat-Shock Proteins
  • Peptide Termination Factors
  • Prions
  • RNQ1 protein, S cerevisiae
  • SUP35 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • HsP104 protein, S cerevisiae