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

Martin-Pastor, M.; Codeseira, Y. B.; Spagnolli, G.; Erana, H.; Fernandez, L. C.; Bravo, S.; Iglesias, A.; Lopez-Moreno, R.; Veiga, S.; Biasini, E.; Sanchez-Pedregal, V. M.; Castilla, J.; Requena, J. R.

doi:10.1101/2020.04.08.032839

bioRxiv · 10.1101/2020.04.08.032839

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

Martin-Pastor, M.·Codeseira, Y. B.·Spagnolli, G.·Erana, H.·Fernandez, L. C.·Bravo, S.·Iglesias, A.·Lopez-Moreno, R.·Veiga, S.·Biasini, E.·Sanchez-Pedregal, V. M.·Castilla, J.·Requena, J. R.

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Abstract

PrPSc, 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 PrPSc 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 PrPSc consisting of a 4-rung {beta} solenoid recently proposed by us. In all cases, our model was compatible with the data. This study shows that elucidation of the structure of PrPSc is within reach using recombinant PrPSc, NMR, and our model as a guiding tool.

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Martin-Pastor, M., Codeseira, Y. B., Spagnolli, G., Erana, H., Fernandez, L. C., Bravo, S., Iglesias, A., Lopez-Moreno, R., Veiga, S., Biasini, E., Sanchez-Pedregal, V. M., Castilla, J., Requena, J. R.. 2020-04-09. Structural features of an infectious recombinant PrPSc prion using solid state NMR. https://doi.org/10.1101/2020.04.08.032839

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