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Science 28 July 2000:
Vol. 289. no. 5479, pp. 595 - 599
DOI: 10.1126/science.289.5479.595
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Research Articles

Evidence for the Prion Hypothesis: Induction of the Yeast [PSI+] Factor by in Vitro- Converted Sup35 Protein

Helmut E. Sparrer,1 Alex Santoso,1 Francis C. Szoka Jr.,2 Jonathan S. Weissman1*

Starting with purified, bacterially produced protein, we have created a [PSI+]-inducing agent based on an altered (prion) conformation of the yeast Sup35 protein. After converting Sup35p to its prion conformation in vitro, we introduced it into the cytoplasm of living yeast using a liposome transformation protocol. Introduction of substoichiometric quantities of converted Sup35p greatly increased the rate of appearance of the well-characterized epigenetic factor [PSI+], which results from self-propagating aggregates of cellular Sup35p. Thus, as predicted by the prion hypothesis, proteins can act as infectious agents by causing self-propagating conformational changes.

1 Department of Cellular and Molecular Pharmacology and
2 Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143-0450, USA.
*   To whom correspondence should be addressed. E-mail: jsw1{at}itsa.ucsf.edu

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