(A) Domain map of Hsp104 shows the location of potentiating mutations in NBD1 (dark blue) and NBD2 (light blue). A503V is in the MD (green). Pink, NTD; brown, CTD.
(B) NBD1 variants suppress α-syn toxicity in yeast. W303aΔhsp104-pAG-303GAL-α-syn-YFP-304GALα-syn-YFP yeast were transformed with Hsp104 variants or vector. Strains were serially diluted 5-fold and spotted in duplicate onto glucose (non-inducing) and galactose (inducing) media.
(C) NBD1 variants do not reduce α-syn expression in yeast. Strains in (B) were induced for 8 h, lysed, and immunoblotted for Hsp104, α-syn, and 3-phosphoglycerate kinase (PGK; loading control).
(D) NBD1 variants suppress α-syn aggregation and mislocalization in yeast. Selected strains in (B) were induced for 8 h and prepared for fluorescence microscopy. Scale bar, 2.5 μm.
(E) α-syn aggregation and localization were quantified by calculating the proportion of cells exhibiting either cytoplasmic aggregates or plasma membrane localization. Values represent means ± SEM (n = 3).
See also Figures S1 and S2.