Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange

Abstract

One of the mysteries in prion research is the structure of the infectious form of mammalian prion protein, PrPSc. We used MS analysis of H/D exchange to examine brain-derived PrPSc. Our data indicate that, contrary to popular models, prion protein conversion involves refolding of the entire region C-terminal to residue ~80–90, and that this region in PrPSc consists of ß-strands and relatively short turns/loops, with no native α-helices present.