Formation of native prions from minimal components in vitro

The conformational change of a host protein, PrP(C), into a disease-associated isoform, PrP(Sc), appears to play a critical role in the pathogenesis of prion diseases such as Creutzfeldt-Jakob disease and scrapie. However, the fundamental mechanism by which infectious prions are produced in neurons remains unknown. To investigate the mechanism of prion formation biochemically, we conducted a series of experiments using the protein misfolding cyclic amplification (PMCA) technique with a preparation containing only native PrP(C) and copurified lipid molecules. These experiments showed that successful PMCA propagation of PrP(Sc) molecules in a purified system requires accessory polyanion molecules. In addition,…

• BW
  Burroughs Wellcome Fund
• DC
  Dartmouth College
• NI
  National Institutes of Health