A systematic survey identifies prions and illuminates sequence features of prionogenic proteins.
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.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Simon
S
Alberti
Randal
R
Halfmann
Oliver
O
King
Atul
A
Kapila
Susan
S
Lindquist
D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism; D001216:Asparagine / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D016681:Genome, Fungal; D005973:Glutamine / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010454:Peptide Termination Factors; D010641:Phenotype; D011328:Prions / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
D000682:Amyloid; D006360:Heat-Shock Proteins; C112006:MOT3 protein, S cerevisiae; D010454:Peptide Termination Factors; D011328:Prions; D020543:Proteome; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D005973:Glutamine; C070972:HsP104 protein, S cerevisiae; D001216:Asparagine