Spectroscopic characterization of conformational differences between PrP C and PrP Sc : an α-helix to β-sheet transition

Abstract

Although no chemical modifications have been found to distinguish the cellular prion protein PrP c from its infectious analogue PrP Sc , spectroscopic methods such as Fourier transform infrared (ftir) spectroscopy reveal a major conformational difference. PrP c is rich in a-helix but is devoid of β-sheet,whereas PrP Sc is high in β-sheet. N-terminal truncation of PrP Sc by 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 Sc from PrP c involves 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.