A systematic survey identifies prions and illuminates sequence features of prionogenic proteins

Cell. 2009 Apr 3;137(1):146-58. doi: 10.1016/j.cell.2009.02.044.


Prions are proteins that convert between structurally and functionally distinct states, one or more of which is transmissible. In yeast, this ability allows them to act as non-Mendelian elements of phenotypic inheritance. To further our understanding of prion biology, we conducted a bioinformatic proteome-wide survey for prionogenic proteins in S. cerevisiae, followed by experimental investigations of 100 prion candidates. We found an unexpected amino acid bias in aggregation-prone candidates and discovered that 19 of these could also form prions. At least one of these prion proteins, Mot3, produces a bona fide prion in its natural context that increases population-level phenotypic heterogeneity. The self-perpetuating states of these proteins present a vast source of heritable phenotypic variation that increases the adaptability of yeast populations to diverse environments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amyloid / metabolism
  • Asparagine / metabolism
  • Cytosol / metabolism
  • Genome, Fungal
  • Glutamine / metabolism
  • Heat-Shock Proteins / metabolism
  • Molecular Sequence Data
  • Peptide Termination Factors
  • Phenotype
  • Prions / analysis*
  • Prions / chemistry
  • Prions / genetics
  • Prions / metabolism
  • Proteome / analysis*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / analysis*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism


  • Amyloid
  • Heat-Shock Proteins
  • MOT3 protein, S cerevisiae
  • Peptide Termination Factors
  • Prions
  • Proteome
  • SUP35 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Glutamine
  • HsP104 protein, S cerevisiae
  • Asparagine