A prion is an infectious protein, a concept derived from studies of scrapie of sheep, and of Kuru, and Creutzfeldt-Jakob disease of man. We discovered that the yeast Saccharomyces cerevisiae can be infected with two prions, two non-chromosomal genetic elements whose properties are those predicted for an infectious protein, not a nucleic acid replicon or a virus. The first, [URE3] is an altered form of Ure2p, the protein product of the chromosomal URE2 gene important in regulation of nitrogen metabolism. The second, [PSI], is an altered form of Sup35p, a subunit of the translation release factor and product of the chromosomal SUP35 gene. We find that Ure2p is more resistant to protease digestion in [URE3] strains than in wild-type strains, supporting the prion model for [URE3]. This protease resistance is not a constant concomitant of derepression of nitrogen metabolism. The N-terminal 65 aminoacid residues of Ure2p is sufficient to propagate [URE3], in the complete absence of the C-terminal nitrogen regulation domain. The overexpression of the URE2 protein, and not the URE2 RNA, is what induces the de novo formation of [URE3]. The C-terminal nitrogen regulation domain is only inactivated when covalently attached to the N-terminal domain, showing that [URE3] is propagated by interactions between the N-terminal prion domains. We have purified Ure2p to near homogeneity and have begun to characterize the difference between the normal and prion forms.
| Shewmaker, Frank; Wickner, Reed B (2006) Ageing in yeast does not enhance prion generation. Yeast 23:1123-8 |
| Edskes, Herman K; Naglieri, Benedetta M; Wickner, Reed B (2006) Nitrogen source and the retrograde signalling pathway affect detection, not generation, of the [URE3] prion. Yeast 23:833-40 |
| Wickner, Reed B; Edskes, Herman K; Shewmaker, Frank (2006) How to find a prion: [URE3], [PSI+] and [beta]. Methods 39:3-8 |
| Baxa, Ulrich; Cheng, Naiqian; Winkler, Dennis C et al. (2005) Filaments of the Ure2p prion protein have a cross-beta core structure. J Struct Biol 150:170-9 |
| Brachmann, Andreas; Baxa, Ulrich; Wickner, Reed Brendon (2005) Prion generation in vitro: amyloid of Ure2p is infectious. EMBO J 24:3082-92 |
| Ross, Eric D; Edskes, Herman K; Terry, Michael J et al. (2005) Primary sequence independence for prion formation. Proc Natl Acad Sci U S A 102:12825-30 |
| Pierce, Michael M; Baxa, Ulrich; Steven, Alasdair C et al. (2005) Is the prion domain of soluble Ure2p unstructured? Biochemistry 44:321-8 |
| Nakayashiki, Toru; Kurtzman, Cletus P; Edskes, Herman K et al. (2005) Yeast prions [URE3] and [PSI+] are diseases. Proc Natl Acad Sci U S A 102:10575-80 |
| Ross, Eric D; Minton, Allen; Wickner, Reed B (2005) Prion domains: sequences, structures and interactions. Nat Cell Biol 7:1039-44 |
| Wickner, Reed B (2005) Scrapie in ancient China? Science 309:874 |
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