Abstract
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.
Highlights
The known amyloid-based prions of Saccharomyces cerevisiae each have multiple heritable forms, called “prion variants” or “prion strains”
Most known prions are self-propagating amyloid forms of normally soluble proteins, there is one non-amyloid prion, namely, the [BETA] prion of yeast, which is the active form of vacuolar protease B [5]. [URE3] [6] is an amyloid-based prion of Ure2p [3,7,8,9,10], whose normal function is the regulation of nitrogen catabolism [11]
When Ure2p is largely converted to amyloid, genes encoding enzymes and transporters needed for using poor nitrogen sources are derepressed in spite of the presence of a good nitrogen source. [PSI+] [12] is an amyloid prion of Sup35p [3,13,14,15,16,17,18,19], a subunit of the translation termination factor [20,21]
Summary
“Prion” means “infectious protein” without the need for an accompanying nucleic acid to transmit the infection [1,2,3]. The in-register parallel β-sheet architecture features rows of sidechains of identical amino acids along the long axis of the filament (Figure 2). We suggest that different prion variants have the folds of the sheet as the molecules already in the filament. We suggest that different prion variants have the folds of (turns in the β-strands) in distinct locations along the peptide chain. Yeast prion prion infectious infectious amyloid amyloid has has Figure the folded folded in-register in-register parallel parallel β β sheet sheet architecture architecture depicted depicted here This structure structure is is maintained maintained by by the the the favorable interactions among identical amino acid side chains that requires them to be in-register. Specific way, but a leg may be broken in many different ways
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