A promiscuous prion: efficient induction of [URE3] prion formation by heterologous prion domains.
The [URE3] and [PSI(+)] prions are the infections amyloid forms of the Saccharomyces cerevisiae proteins Ure2p and Sup35p, respectively. Randomizing the order of the amino acids in the Ure2 and Sup35 prion domains while retaining amino acid composition does not block prion formation, indicating that amino acid composition, not primary sequence, is the predominant feature driving [URE3] and [PSI(+)] formation. Here we show that Ure2p promiscuously interacts with various compositionally similar proteins to influence [URE3] levels. Overexpression of scrambled Ure2p prion domains efficiently increases de novo formation of wild-type [URE3] in vivo. In vitro, amyloid aggregates of the scrambled prion domains efficiently seed wild-type Ure2p amyloid formation, suggesting that the wild-type and scrambled prion domains can directly interact to seed prion formation. To test whether interactions between Ure2p and naturally occurring yeast proteins could similarly affect [URE3] formation, we identified yeast proteins with domains that are compositionally similar to the Ure2p prion domain. Remarkably, all but one of these domains were also able to efficiently increase [URE3] formation. These results suggest that a wide variety of proteins could potentially affect [URE3] formation.
Ross
Carley D
CD
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, USA.
McCarty
Blake R
BR
Hamilton
Michael
M
Ben-Hur
Asa
A
Ross
Eric D
ED
D000682:Amyloid / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D000682:Amyloid; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae