Proteins Rule! StanPrusinerPrion Biology and Diseases1999Cold Spring Harbor Laboratory PressCold Spring Harbor, NY710 pp. $125.00

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Prion variants, species barriers, generation and propagation

Prion variants faithfully propagate across species barriers, but if the barrier is too high, new variants (mutants) are selected, as shown in a recent BMC Biology report. Protein sequence alteration can prevent accurate structural templating at filament ends producing prion variants

Prion Variants of Yeast are Numerous, Mutable, and Segregate on Growth, Affecting Prion Pathogenesis, Transmission Barriers, and Sensitivity to Anti-Prion Systems

The known amyloid-based prions of Saccharomyces cerevisiae each have multiple heritable forms, called “prion variants” or “prion strains”. These variants, all based on the same prion protein sequence, differ in their biological properties and their detailed amyloid structures, although each of the few examined to date have an in-register parallel folded β sheet architecture. Here, we review the range of biological properties of yeast prion variants, factors affecting their generation and propagation, the interaction of prion variants with each other, the mutability of prions, and their segregation during mitotic growth. After early differentiation between strong and weak stable and unstable variants, the parameters distinguishing the variants has dramatically increased, only occasionally correlating with the strong/weak paradigm. A sensitivity to inter- and intraspecies barriers, anti-prion systems, and chaperone deficiencies or excesses and other factors all have dramatic selective effects on prion variants. Recent studies of anti-prion systems, which cure prions in wild strains, have revealed an enormous array of new variants, normally eliminated as they arise and so not previously studied. This work suggests that defects in the anti-prion systems, analogous to immune deficiencies, may be at the root of some human amyloidoses

Supplemental Material for Edskes et al., 2018

Supplemental Methods_figures_tables.pdf - Provides a detailed description of the culture conditions, induction of <i>Hermes</i> transposition, selection of colonies carrying a transposition, extraction of cellular DNA, PCR amplification and isolation of the junction points between transposon and chromosomal insertion site, next-generation sequencing of these sites, and analysis of the data by visual display and by counting insertions per open reading frame. <br><br> Exon Intron Counts.xlsx - Gives the insertions in every yeast open reading frame, distinguishing exons from introns where appropriate.<br><br>Sorted Hits.xlsx - Gives prominent hits sorted by functional group, “TY gag-pol Counts.xlsx comparing insertions in the Ty retrotransposons at different locations in the genome. <br><br>Count Insertions in ORFs and Introns.txt - The Python program used for counting insertions. <br><br>LUGsIGV-InsertDistributions.pptx - Is a slide show of insert distributions in each of 500 genes for which insertions were recovered more frequently in [ure-o] than in [URE3] cultures