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Updated: Jun 26, 2026

High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Yeast prions: evolution of the prion concept
Reed B Wickner1, Herman K Edskes, Frank Shewmaker
1Laboratory of Biochemistry and Genetics, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0830, USA. wickner@helix.nih.gov
Prions, or infectious proteins, can act as genes in yeast. Their prion domains can be randomized, suggesting amino acid content, not sequence, determines prion formation.
Area of Science:
- Molecular Biology
- Protein Chemistry
- Genetics
Background:
- Prions are infectious proteins analogous to the scrapie agent.
- Prions have been identified in Saccharomyces cerevisiae and Podospora anserina.
- These prions function as genes, similar to nucleic acids acting as enzymes.
Purpose of the Study:
- To investigate the nature of prions in yeast.
- To understand the determinants of prion formation and propagation.
Main Methods:
- Identification and characterization of specific prions: [URE3], [PSI(+)], [PIN(+)], and [Het-s].
- Analysis of prion domains, including randomization of amino acid sequences.
- Structural analysis suggesting amyloid formation with parallel in-register beta-sheet structure.
Main Results:
- Identified four yeast prions: [URE3] (Ure2p), [PSI(+)] (Sup35p), [PIN(+)] (Rnq1p), and [Het-s] (HET-s protein).
- Demonstrated that prion domains of Ure2p and Sup35p can be randomized without losing prion-forming ability.
- Indicated that amino acid content, rather than specific sequence, determines prion formation.
- Structural studies suggest a parallel in-register beta-sheet amyloid structure.
Conclusions:
- Yeast prions ([URE3], [PSI(+)], [PIN(+)], [Het-s]) are self-propagating amyloids.
- Prion formation is primarily determined by amino acid composition, not sequence.
- The shuffleability of prion domains supports an amyloid structure with beta-sheet characteristics.
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