Hsp104 Inhibition Blocks Sup35-GFP^{[<i>PSI+</i>]} Remodeling and Creates a Segregation Bias for Sup35-GFP Complexes

<div><p><i>MAT<b>a</b></i> [<i>psi⁻</i>] haploids expressing untagged <i>SUP35</i> and <i>SUP35-GFP</i> from P<i>_MFA1</i> were mated to <i>MATα</i> [<i>PSI⁺</i>] haploids constitutively expressing untagged <i>SUP35</i> in the presence or absence of functional Hsp104. For each cross, a zygote (left) and a microcolony derived from that zygote (right) are shown.</p> <p>(A) Representative images from a wild-type cross (SY360 × SY581) are shown (<i>n</i> = 10).</p> <p>(B) Shown are representative images (<i>n</i> = 5) from a <i>KTKT</i> × wild-type cross (SY876 × SY581). The originating zygote is outlined in the DIC image and marked with an arrow in the microcolony.</p> <p>(C) Shown are representative images (<i>n</i> = 6) of a wild-type cross (SY360 × SY581) in the presence of GdnHCl.</p> <p>(D) A model for Hsp104-dependent remodeling of prion complexes. Soluble Sup35-GFP^{[<i>psi−</i>]} (green ball and stick) is remodeled to the prion form (black and green ball and loop) upon encountering Sup35^{[<i>PSI+</i>]} in an Hsp104-independent process. These complexes are rapidly fragmented by Hsp104 (white hexamer) to smaller complexes, which then efficiently incorporate soluble Sup35^{[<i>psi−</i>]} (black ball and stick), effectively redistributing existing Sup35-GFP^{[<i>PSI+</i>]}.</p>