Amyloid formation of a yeast prion determinant
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The [PSI +] factor of the yeast Saccharomyces cerevisiae is a cytoplasmic, epigenetic regulator of translation termination and can be transmitted from mother to daughter cells in a non-Mendelian manner. The transmission is caused by self-perpetuating noncovalent changes in the physical state of the protein determinant Sup35p, rather than by changes in its encoding gene. This phenomenon is reminiscent of the protein-only mechanism proposed for the infectious agent in a group of unusual, fatal neurodegenerative diseases in mammals. These diseases, known as prion diseases, are thought to involve a self-perpetuating change in the conformation of the prion protein (PrP) from a soluble form to one reflecting amyloid structure. In contrast to mammalian PrPs, Sup35p[PSI+] is not associated with disease in yeast and is not infectious for humans. Because of the mechanistic similarities of transmission of a specific, nonsoluble protein conformation, the epigenetic inheritance of [PSI +] in yeast was called a yeast prion phenomenon, and the yeast prion hypothesis was born. The elucidation of the mechanism by which alternative protein conformations transmit their structural information is key to understanding how proteins function as elements of epigenetic inheritance and how amyloidogenic conformations can be propagated. Yeast provides an ideal system to analyze both the epigenetic traits in vivo and the phenomenon of amyloid formation in vitro. The combination of these tools will help to determine the general mechanism of prion and amyloid appearance and propagation.
Index EntriesNeurodegenerative disease PrP Sup35p TSE yeast prion
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