Significance Expansion of polyglutamine tracts in at least nine proteins causes neurodegeneration. Although the pathology caused by each protein is different, there must be common features of the polyglutamine expansion that contribute to toxicity. We modeled polyglutamine toxicity in yeast by expressing a 103-glutamine expanded fragment of huntingtin (Htt103Q) and screened the yeast genome to identify proteins that alter this toxicity. Surprisingly, our suppressors were proteins containing glutamine- and asparagine-rich segments typical of prion proteins. When we expressed just these segments with Htt103Q, the two proteins formed large, coaggregated particles, and smaller, more toxic aggregated forms were absent. Proteins with such segments may interact with polyQ-expanded proteins and thereby modulate their toxicity. These interaction partners provide targets for therapeutic intervention.