Recently, a novel mode of inheritance has been described in the yeast Saccharomyces cerevisiae. The mechanism is based on the prion hypothesis, which posits that self-perpetuating changes in the conformation of single protein, PrP, underlie the severe neurodegeneration associated with the transmissible spongiform enchephalopathies in mammals. In yeast, two prions, [URE3] and [PSI+], have been identified, but these factors confer unique phenotypes rather than disease to the organism. In each case, the prion-associated phenotype has been linked to alternative conformations of the Ure2 and Sup35 proteins. Remarkably, Ure2 and Sup35 proteins existing in the alternative conformations have the unique capacity to transmit this physical state to the newly synthesized protein in vivo. Thus, a mechanism exists to ensure replication of the conformational information that underlies protein-only inheritance. We have characterized the mechanism by which Sup35 conformational information is replicated in vitro. The assembly of amyloid fibres by a region of Sup35 encompassing the N-terminal 254 amino acids faithfully recapitulates the in vivo propagation of [PSI+]. Mutations that alter [PSI+] inheritance in vivo change the kinetics of amyloid assembly in vitro in a complementary fashion, and lysates from [PSI+] cells, but not [psi-] cells, accelerate assembly in vitro. Using this system we propose a mechanism by which the alternative conformation of Sup35 is adopted by an unstructured oilgomeric intermediate at the time of assembly.
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August 2001
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Conference Article|
August 01 2001
Self-perpetuating changes in Sup35 protein conformation as a mechanism of heredity in yeast
Tricia R. Serio;
Tricia R. Serio
*Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, U.S.A.
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Anil G. Cashikar;
Anil G. Cashikar
†Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, U.S.A.
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Anthony S. Kowal;
Anthony S. Kowal
†Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, U.S.A.
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George J. Sawicki;
George J. Sawicki
†Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, U.S.A.
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Susan L. Lindquist
Susan L. Lindquist
1
*Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, U.S.A.
†Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, U.S.A.
1To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Online ISSN: 1744-1439
Print ISSN: 0067-8694
© 2001 The Biochemical Society
2001
Biochem Soc Symp (2001) 68: 35–43.
Citation
Alan Berry, Sheena E. Radford, Tricia R. Serio, Anil G. Cashikar, Anthony S. Kowal, George J. Sawicki, Susan L. Lindquist; Self-perpetuating changes in Sup35 protein conformation as a mechanism of heredity in yeast. Biochem Soc Symp 1 August 2001; 68 35–43. doi: https://doi.org/10.1042/bss0680035
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