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Perturbation of the secondary structure of the scrapie prion protein under conditions that alter infectivity.

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  • 1. Department of Neurology, University of California, San Francisco 94143.
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    • Gasset M 1
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Proceedings of the National Academy of Sciences of the United States of America, 01 Jan 1993, 90(1):1-5
https://doi.org/10.1073/pnas.90.1.1 PMID: 8419912 PMCID: PMC45587

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Abstract 

Limited proteolysis of the scrapie prion protein (PrPSc) generates PrP 27-30, which polymerizes into amyloid. By attenuated total reflection-Fourier transform infrared spectroscopy, PrP 27-30 polymers contained 54% beta-sheet, 25% alpha-helix, 10% turns, and 11% random coil; dispersion into detergent-lipid-protein-complexes preserved infectivity and secondary structure. Almost 60% of the beta-sheet was low-frequency infrared-absorbing, reflecting intermolecular aggregation. Decreased low-frequency beta-sheet and increased turn content were found after SDS/PAGE, which disassembled the amyloid polymers, denatured PrP 27-30, and diminished scrapie infectivity. Acid-induced transitions were reversible, whereas alkali produced an irreversible transition centered at pH 10 under conditions that diminished infectivity. Whether PrPSc synthesis involves a transition in the secondary structure of one or more domains of the cellular prion protein from alpha-helical, random coil, or turn into beta-sheet remains to be established.

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Proc Natl Acad Sci U S A. 1993 Jan 1; 90(1): 1–5.
PMCID: PMC45587
PMID: 8419912

Perturbation of the secondary structure of the scrapie prion protein under conditions that alter infectivity.

M Gasset, M A Baldwin, R J Fletterick, and S B Prusiner
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Abstract

Limited proteolysis of the scrapie prion protein (PrPSc) generates PrP 27-30, which polymerizes into amyloid. By attenuated total reflection-Fourier transform infrared spectroscopy, PrP 27-30 polymers contained 54% beta-sheet, 25% alpha-helix, 10% turns, and 11% random coil; dispersion into detergent-lipid-protein-complexes preserved infectivity and secondary structure. Almost 60% of the beta-sheet was low-frequency infrared-absorbing, reflecting intermolecular aggregation. Decreased low-frequency beta-sheet and increased turn content were found after SDS/PAGE, which disassembled the amyloid polymers, denatured PrP 27-30, and diminished scrapie infectivity. Acid-induced transitions were reversible, whereas alkali produced an irreversible transition centered at pH 10 under conditions that diminished infectivity. Whether PrPSc synthesis involves a transition in the secondary structure of one or more domains of the cellular prion protein from alpha-helical, random coil, or turn into beta-sheet remains to be established.

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Selected References

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