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: 4.84). 10/2008; 30(10):955-64. DOI: 10.1002/bies.20821
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Frank Shewmaker, Jan 31, 2014
  • Source
    [Show abstract] [Hide abstract]
    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.
    Genetics 03/2011; 188(1):81-90. DOI:10.1534/genetics.111.127217 · 4.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    Genetics 02/2009; 181(3):1159-67. DOI:10.1534/genetics.108.099929 · 4.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper presents a high-frequency current-controlled relaxation oscillator designed for ultra-low voltage supply (0.9 V). The choosen relaxation oscillator topology provides both high frequency and low noise characteristic. Simulated results are verified by measurements on a full-custom integrated circuit. The tuning range extends from 1 to 180 MHz with supply current limited to 1.1 mA. At a 200 kHz off set from the oscillator frequency, the measured phase noise is-89 dBc/Hz.
    Solid-State Circuits Conference, 1997. ESSCIRC '97. Proceedings of the 23rd European; 10/1997