![]() It is thought that the accumulation of misfolded proteins, including misfolded Sup35p, under these stress conditions may initiate prion formation. Prion formation has also been shown to be increased by exposure to environmental stress ( Tyedmers et al., 2008). These extra repeats have been suggested to more readily direct the assembly of Sup35 proteins into ordered complexes. An expansion of an oligopeptide repeat within the N-terminal prion forming region of Sup35 increases prion formation ( Liu and Lindquist, 1999). Despite this low level, several approaches can increase the rate of de novo formation. Analysis of the Sup35 prion, or, found that the spontaneous rate of formation is less than 1 in 1 million cells per generation ( Lund and Cox, 1981 Allen et al., 2005 Lancaster et al., 2010). Spontaneous prion formation in yeast is quite rare. Work in yeast has provided important insights into how prions form and when they become infectious. The process by which these proteins initially misfold and aggregate to form infectious particles is still unclear. In each case, the monomeric protein misfolds into an alternate stable conformation that in turn is able to convert normal copies of the protein to a misfolded form that is prone to aggregation. Several proteins have been shown to form prions in yeast, including Sup35p, Ure2p, Rnq1p, Swi1p, Cyc8p, and Mot3p (reviewed in Liebman and Chernoff, 2012). Prions are misfolded aggregated proteins that are infectious. We speculate that changes in the cellular milieu in vps5Δ strains may reduce the cell's ability to efficiently recruit and sequester newly formed prion particles into central deposition sites, resulting in toxicity. ![]() Instead of large immobile aggregates, vps5Δ strains have additional population of small mobile foci. However using green fluorescent protein fusions, we observe that the assembly of fluorescent cytoplasmic aggregates during prion formation is different in vps5Δ strains. Here, we show that newly made oligomer formation and infectivity of vps5Δ lysates are similar to wildtype strains. Previous work shows that toxicity is associated with prion formation and this toxicity is exacerbated by deletion of the VPS5 gene. Our recent work suggests that SDS-resistant oligomers arise and remodel early during the prion formation process, and lysates containing these newly formed oligomers are infectious. The study of the yeast prion has provided valuable insights into how prions form and why they are toxic. It is believed that the oligomers contribute to cytotoxicity, although genetic and environmental factors have also been shown to have additional roles. Prions are infectious misfolded proteins that assemble into oligomers and large aggregates, and are associated with neurodegeneration.
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