Protein inheritance (prions) based on parallel in-register β-sheet amyloid structures

Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA.
BioEssays (Impact Factor: 4.73). 10/2008; 30(10):955-64. DOI: 10.1002/bies.20821
Source: PubMed


Most prions (infectious proteins) are self-propagating amyloids (filamentous protein multimers), and have been found in both mammals and fungal species. The prions [URE3] and [PSI+] of yeast are disease agents of Saccharomyces cerevisiae while [Het-s] of Podospora anserina may serve a normal cellular function. The parallel in-register beta-sheet structure shown by prion amyloids makes possible a templating action at the end of filaments which explains the faithful transmission of variant differences in these molecules. This property of self-reproduction, in turn, allows these proteins to act as de facto genes, encoding heritable information.

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Available from: Frank Shewmaker, Jan 31, 2014
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    • "However, these proximal 93 amino acids allow Ure2p to form a prion, an infectious inactive form of the protein (Masison and Wickner 1995; Wickner 1994). The first 65 amino acids have been shown sufficient to propagate the prion form of Ure2p (Masison et al. 1997), and form infectious amyloid with a parallel in-register b-sheet structure (Brachmann et al. 2005; Baxa et al. 2007; reviewed in Wickner et al. 2008). The C-terminal domains of the Ure2 proteins of ascomycete yeasts, starting at amino acid 100 of S. cerevisiae , show strong conservation (Edskes and Wickner 2002; Baudin-Baillieu et al. 2003; Harrison et al. 2007). "
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    ABSTRACT: [URE3] is a prion (infectious protein) of the Saccharomyces cerevisiae Ure2p, a regulator of nitrogen catabolism. We show that wild S. paradoxus can be infected with a [URE3] prion, supporting the use of S. cerevisiae as a prion test bed. We find that the Ure2p of Candida albicans and C. glabrata also regulate nitrogen catabolism. Conservation of amino acid sequence within the prion domain of Ure2p has been proposed as evidence that the [URE3] prion helps its host. We show that the C. albicans Ure2p, which does not conserve this sequence, can nonetheless form a [URE3] prion in S. cerevisiae, but the C. glabrata Ure2p, which does have the conserved sequence, cannot form [URE3] as judged by its performance in S. cerevisiae. These results suggest that the sequence is not conserved to preserve prion forming ability.
    Full-text · Article · Mar 2011 · Genetics
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    • "The presence of the [URE3] prion is thus assayed by the uptake by the Ure2- controlled Dal5p transporter of USA or by activity of ADE2 driven by the DAL5 promoter (Lacroute 1971; Schlumpberger et al. 2001). The [URE3], [PSI 1 ], and [PIN 1 ] prions are based on self-propagating amyloids of their respective proteins (King and Diaz-Avalos 2004; Tanaka et al. 2004; Brachmann et al. 2005; Patel and Liebman 2007; reviewed in Wickner et al. 2008b). Species barriers have been described for [PSI 1 ] (Chernoff et al. 2000; Kushnirov et al. 2000; Santoso et al. 2000; Chen et al. 2007) and [URE3] (Edskes and Wickner 2002; Baudin-Baillieu et al. 2003) and prion variants have been recognized in yeast prions [PSI 1 ], [URE3], and [PIN 1 ] (Derkatch et al. 1996; Schlumpberger et al. 2001; Bradley et al. 2002; Brachmann et al. 2005). "
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    ABSTRACT: As hamster scrapie cannot infect mice, due to sequence differences in their PrP proteins, we find "species barriers" to transmission of the [URE3] prion in Saccharomyces cerevisiae among Ure2 proteins of S. cerevisiae, paradoxus, bayanus, cariocanus, and mikatae on the basis of differences among their Ure2p prion domain sequences. The rapid variation of the N-terminal Ure2p prion domains results in protection against the detrimental effects of infection by a prion, just as the PrP residue 129 Met/Val polymorphism may have arisen to protect humans from the effects of cannibalism. Just as spread of bovine spongiform encephalopathy prion variant is less impaired by species barriers than is sheep scrapie, we find that some [URE3] prion variants are infectious to another yeast species while other variants (with the identical amino acid sequence) are not. The species barrier is thus prion variant dependent as in mammals. [URE3] prion variant characteristics are maintained even on passage through the Ure2p of another species. Ure2p of Saccharomyces castelli has an N-terminal Q/N-rich "prion domain" but does not form prions (in S. cerevisiae) and is not infected with [URE3] from Ure2p of other Saccharomyces. This implies that conservation of its prion domain is not for the purpose of forming prions. Indeed the Ure2p prion domain has been shown to be important, though not essential, for the nitrogen catabolism regulatory role of the protein.
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