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.