Conversion scrapie

  • Pan K
  • Baldwin M
  • Nguyen J
 et al. 
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Abstract

Prions are composed largely, if not entirely, by a post-translational process that probably of prion protein (PrPsc in the case of scrapie). Although the formation of PrPs from the cellular prion protein (PrPc) is a post-translational process, no candidate chemical modification was identified, suggesting that a conformational change fea- tures in PrPsc synthesis. To assess this possibility, we purified both PrPC and PrPsc by using nondenaturing procedures and determined the secondary structure ofeach. Fourier-transform infrared (FTIR) spectroscopy demonstrated that PrPC has a high a-helix content (42%) and no (3sheet (3%), findings that were confirmed by circular dichroism measurements. In con- trast, the -sheet content of PrPSc was 43% and the a-helix 30% as measured by FTIR. As determined in earlier studies, N-terminally truncated PrPsc derived by limited proteolysis, designated PrP 27-30, has an even higher -sheet content (54%) and a lower a-helix content (21%). Neither PrPC nor PrPsc formed aggregates detectable by electron microscopy, while PrP 27-30 polymerized into rod-shaped amyloids. While the foregoing rmdings argue that the conversion of a-helices into 1-sheets underlies the formation of PrPsc, we cannot eliminate the possibility that an undetected chemical modifi- cation of a small fraction of PrPSC initiates this process. Since PrPsc seems to be the only component of the "infectious" prion particle, it is Ihkely that this conformational transition is a fundamental event in the propagation of prions.

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Authors

  • Keh-ming Pan

  • Michael Baldwin

  • Jack Nguyen

  • Maria Gasset

  • a N a Serban

  • Darlene Groth

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