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

Abstract

Abstract 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 conditions into a β-hairpin like tertiary structure, whereas, in the non-pathogenic form of protein and in trifuoroethanol (TFE), the region is engaged in largely α-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.