Chaperones that cure yeast artificial [PSI+] and their prion-specific effects

The PSI(+)] nonsense-suppressor determinant of Saccharomyces cerevisiae results from the ability of Sup35 (eRF3) translation termination factor to undergo prion-like aggregation 1]. Although this process is autocatalytic, in vivo it depends on the chaperone Hsp104, whose lack or overexpression can cure PSI(+)] 2]. Overproduction of the chaperone protein Ssb1 increased the PSI(+)] curing by excess Hsp104, although it had no effect on its own, and excess chaperone protein Ssa1 protected PSI(+)] against Hsp104 3,4]. We used an artificial PSI(+)(PS)] based on the Sup35 prion-forming domain from yeast Pichia methanolica 5] to find other prion-curing factors. Both PSI(+)(PS)] and PSI(+)] have prion 'strains', differing in their suppressor efficiency and mitotic stability. We show that PSI(+)(PS)] and a 'weak' strain of PSI(+)] can be cured by overexpression of chaperones Ssa1, Ssb1 and Ydj1. The ability of different chaperones to cure PSI(+)(PS)] showed significant prion strain specificity, which could be related to variation in Sup35 prion structure. Our results imply that homologs of these chaperones may be active against mammalian prion and amyloid diseases.