Spectroscopic characterization of conformational differences between PrPCand PrPSc: an α-helix to β-sheet transition

Abstract

Although no chemical modifications have been found to distinguish the cellular prion protein PrP^cfrom its infectious analogue PrP^Sc, spectroscopic methods such as Fourier transform infrared (ftir) spectroscopy reveal a major conformational difference. PrP^cis rich in a-helix but is devoid of β-sheet,whereas PrP^Scis high in β-sheet. N-terminal truncation of PrP^Scby limited proteolysis does not destroy infectivity but it increases the β-sheet content and shifts the ftir absorption to lower frequencies, typical of the cross β-pleated sheets of amyloids. Thus the formation of PrP^Scfrom PrP^cinvolves a conformational transition in which one or more x-helical regions of the protein is converted to β-sheet. This transition is mimicked by synthetic peptides, allowing predictions of domains of PrP involved in prion diseases.