Conformation preserved in a weak-to-strong or strong-to-weak [PSI⁺] conversion during transmission to Sup35 prion variants

The cytoplasmic [PSI⁺] element of budding yeast represents the prion conformation of translation release factor Sup35. Much interest lies in understanding how prions are able to generate variation in isogenic strains. Recent observations suggest that a single prion domain, PrD, is able to adopt several conformations that account for prion strains. We report novel PrD variants of Sup35 that convert weak [PSI⁺] to strong [PSI⁺], and vice versa, upon transmission from wild-type Sup35. During the transmission from wild-type Sup35 to variant Sup35s, no conformational changes were detected by proteolytic fingerprinting and the original [PSI⁺] strain was remembered upon return to wild-type Sup35. These findings suggest that during transmission to variant Sup35s, the [PSI⁺] phenotype is variable while the original conformation is remembered. A mechanism of "conformational memory" to remember specific [PSI⁺] conformations during transmission is proposed.