Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.
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- K M Pan
- Department of Neurology, University of California, San Francisco 94143.
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- M Baldwin
- Department of Neurology, University of California, San Francisco 94143.
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- J Nguyen
- Department of Neurology, University of California, San Francisco 94143.
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- M Gasset
- Department of Neurology, University of California, San Francisco 94143.
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- A Serban
- Department of Neurology, University of California, San Francisco 94143.
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- D Groth
- Department of Neurology, University of California, San Francisco 94143.
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- I Mehlhorn
- Department of Neurology, University of California, San Francisco 94143.
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- Z Huang
- Department of Neurology, University of California, San Francisco 94143.
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- R J Fletterick
- Department of Neurology, University of California, San Francisco 94143.
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- F E Cohen
- Department of Neurology, University of California, San Francisco 94143.
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<jats:p>Prions are composed largely, if not entirely, of prion protein (PrPSc in the case of scrapie). Although the formation of PrPSc from the cellular prion protein (PrPC) is a post-translational process, no candidate chemical modification was identified, suggesting that a conformational change features in PrPSc synthesis. To assess this possibility, we purified both PrPC and PrPSc by using nondenaturing procedures and determined the secondary structure of each. Fourier-transform infrared (FTIR) spectroscopy demonstrated that PrPC has a high alpha-helix content (42%) and no beta-sheet (3%), findings that were confirmed by circular dichroism measurements. In contrast, the beta-sheet content of PrPSc was 43% and the alpha-helix 30% as measured by FTIR. As determined in earlier studies, N-terminally truncated PrPSc derived by limited proteolysis, designated PrP 27-30, has an even higher beta-sheet content (54%) and a lower alpha-helix content (21%). Neither PrPC nor PrPSc formed aggregates detectable by electron microscopy, while PrP 27-30 polymerized into rod-shaped amyloids. While the foregoing findings argue that the conversion of alpha-helices into beta-sheets underlies the formation of PrPSc, we cannot eliminate the possibility that an undetected chemical modification of a small fraction of PrPSc initiates this process. Since PrPSc seems to be the only component of the "infectious" prion particle, it is likely that this conformational transition is a fundamental event in the propagation of prions.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 90 (23), 10962-10966, 1993-12
Proceedings of the National Academy of Sciences
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詳細情報
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- CRID
- 1362262945460140160
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- NII論文ID
- 80007374264
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- NII書誌ID
- AA10808769
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- ISSN
- 10916490
- 00278424
- http://id.crossref.org/issn/00278424
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