Yeast prions: evolution of the prion concept.
Prions (infectious proteins) analogous to the scrapie agent have been identified in Saccharomyces cerevisiae and Podospora anserina based on their special genetic characteristics. Each is a protein acting as a gene, much like nucleic acids have been shown to act as enzymes. The [URE3], [PSI(+)], [PIN(+)] and [Het-s] prions are self-propagating amyloids of Ure2p, Sup35p, Rnq1p and the HET-s protein, respectively. The [beta] and [C] prions are enzymes whose precursor activation requires their own active form. [URE3] and [PSI(+)] are clearly diseases, while [Het-s] and [beta] carry out normal cell functions. Surprisingly, the prion domains of Ure2p and Sup35p can be randomized without loss of ability to become a prion. Thus amino acid content and not sequence determine these prions. Shuffleability also suggests amyloids with a parallel in-register beta-sheet structure.
Wickner
Reed B
RB
Laboratory 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
Edskes
Herman K
HK
Shewmaker
Frank
F
Nakayashiki
Toru
T
Engel
Abbi
A
McCann
Linsay
L
Kryndushkin
Dmitry
D
D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D048468:Podospora / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D000682:Amyloid; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins