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

One of the mysteries in prion research is the structure of the infectious form of mammalian prion protein PrPSc. Here we used mass spectrometry analysis of hydrogen-deuterium exchange to examine brain-derived PrPSc. Our data indicate that, contrary to popular models, prion-protein conversion involves refolding of the entire region from residue similar to 80-90 to the C-terminus, which in PrPSc consists of beta-strands and relatively short turns and/or loops, with no native alpha-helices present.