Conversion of PrP to a Self-Perpetuating PrP Sc -like Conformation in the Cytosol
Top Cited Papers
- 29 November 2002
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 298 (5599) , 1785-1788
- https://doi.org/10.1126/science.1073619
Abstract
A rare conformation of the prion protein, PrP Sc , is found only in mammals with transmissible prion diseases and represents either the infectious agent itself or a major component of it. The mechanism for initiating PrP Sc formation is unknown. We report that PrP retrogradely transported out of the endoplasmic reticulum produced both amorphous aggregates and a PrP Sc -like conformation in the cytosol. The distribution between these forms correlated with the rate of appearance in the cytosol. Once conversion to the PrP Sc -like conformation occurred, it was sustained. Thus, PrP has an inherent capacity to promote its own conformational conversion in mammalian cells. These observations might explain the origin of PrP Sc .Keywords
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