Structural features of an infectious recombinant PrPSc prion using solid state NMR

ABSTRACT

PrP ^Sc, the first described and most notorious prion, is the only protein known to cause epidemics of deadly disease. Its properties are encoded in its unique structure. Here we report a first solid state NMR study of a uniformly labelled (U- ¹³C, ¹⁵N)-Bank vole (BV) infectious recombinant PrP ^Sc prion. C-C, C-H and N-H spectra were obtained with MAS rotation of the sample at up to 60 kHz. We obtained amino acid-type secondary structure information and used it to challenge a physically plausible atomistic model of PrP ^Sc consisting of a 4-rung β solenoid recently proposed by us. In all cases, our model was compatible with the data. This study shows that elucidation of the structure of PrP ^Sc is within reach using recombinant PrP ^Sc, NMR, and our model as a guiding tool.