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Paul E. Bendheim, Anna Potempska, Richard J. Kascsak, David C. Bolton, Purification and Partial Characterization of the Normal Cellular Homologue of the Scrapie Agent Protein, The Journal of Infectious Diseases, Volume 158, Issue 6, December 1988, Pages 1198–1208, https://doi.org/10.1093/infdis/158.6.1198
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Abstract
The scrapie agent protein (Sp33-37) is a degradation-resistant protein that aggregates into fibrils and amyloid plaques. This protein is derived from a normal cellular protein (Cp33-37). Understanding the mechanism responsible for the conversion of Cp33-37 to Sp33-37 may explain scrapie agent replication. Cp33-37 was extracted from normal hamster brain and purified 2700-fold by an immunoaffinity method. Both Cp33-37 purified from normal hamster brain and Sp33-37 purified from scrapie-affected hamster brain had apparent masses of 33-37 kilodaltons and displayed microheterogeneity characteristic of glycoproteins. Cp33-37 was completely digested by proteinase K under conditions that resulted in conversion of Sp33-37 to the protease-resistant fragment PrP27-30. Cp33-37 did not cause scrapie when inoculated intracerebrally into hamsters. Fractions containing purified Sp33-37 had average titers of > 1011 LD50 of the scrapie agent/mg of protein; these titers were not diminished by proteinase K. These results indicate that altered sensitivity to proteolysis in vitro reflects an intrinsic difference between Sp33-37 and Cp33-37.