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Transmissible spongiform encephalopathies (TSEs) in humans and animals are attributed to protein-only infectious agents, called prions. Prions have been proposed to arise from the conformational conversion of the cellular protein PrPC into a misfolded form (e.g., PrPSc for scrapie), which precipitates into aggregates and fibrils. It has been proposed that the conversion process is triggered by the interaction of the infectious form (PrPSc) with the cellular form (PrPC) or might result from a mutation in the gene for PrPC. However, until recently, all efforts to reproduce this process in vitro had failed, suggesting that host factors are necessary for prion replication. In this review we discuss recent findings such as the cellular factors that might be involved in the conformational conversion of prion proteins and the potential mechanisms by which they could operate.
Index EntriesPrPC PrPSc prion conversion transconformation cofactor
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- Bogdanov M. and Dowhan W. (1999) Lipid-assisted protein folding. J. Biol. Chem. 274, 36,827–36,830.Google Scholar
- Borchelt D. R., Taraboulos A., and Prusiner S. B. (1992) Evidence for synthesis of scrapie prion proteins in the endocytic pathway. J. Biol. Chem. 267, 16,188–16,199.Google Scholar
- Castilla J., Gutierrez-Adan A., Brun A., Pintado B., Parra B., Ramirez M. A., et al. (2004) Different behavior toward bovine spongiform encephalopathy infection of bovine prionprotein transgenic mice with one extra repeat octapeptide insert mutation. J. Neurosci. 24, 2156–2164.PubMedCrossRefGoogle Scholar
- Jin T., Gu Y., Zanusso G., Sy M., Kumar A., Cohen M., Gambetti P., and Singh N. (2000) The chaperone protein BiPbinds to a mutant prion protein and mediates its degradation by the proteasome. J. Biol. Chem. 275, 38,699–38,704.Google Scholar
- Pan K. M., Baldwin M., Nguyen J., Gasset M., Serban A., Groth D., et al. (1993) Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc. Natl. Acad. Sci. U. S. A. 90, 10,962–10,966.Google Scholar
- Riesner D., Kellings K., Post K., Wille H., Serban H., Groth D., et al. (1996) Disruption of prion rods gene-rates 10-nm spherical particles having high alphahelical content and lacking scrapie infectivity. J. Virol. 10, 1714–1722.Google Scholar