Solution structure of the sheep prion PrP[142-166]: a possible site for the conformational conversion of prion protein

摘要

In order to get deeper insight into the molecular forces responsible for prion pathogenic conversion, conformational properties of a synthetic linear peptide derived from the globular core of sheep prion protein were studied by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopies. The studied peptide encompassing the [142-166] (in human numbering) region of sheep prion protein, folds in physiological condition into a #beta#-hairpin like tertiary structure, whereas, in the non-pathogenic form of protein and in trifuoroethanol (TFE), the region is engaged in largely #alpha#-helical conformation. Such structural duality of the fragment indicates a possible transconformational site within prion protein and may explain one of the early structural causes of prion diseases.