Kaneko, K.Peretz, DavidPan, K. K.Blochberger, Thomas C.Wille, H.Gabizon, R.Griffith, O. H.Cohen, F. E.Baldwin, Michael A.Prusiner, Stanley B.2016-06-032016-06-031995-11Kaneko, K., Peretz, D., Pan, K.-K., Blochberger, T. C., Wille, H., Gabizon, R., Griffith, O. H., Cohen, F. E., Baldwin, M. A., and Prusiner, S. B. (1995) Prion protein (Pr) synthetic peptides induce cellular PrP to acquire properties of the scrapie isoform. Proc. Natl. Acad. Sci. USA, 92, 11160-11164.https://hdl.handle.net/1794/199345 pagesConversion of the cellular isoform of prion protein (PrPc) into the scrapie isoform (PrPSc) involves an increase in the /3-sheet content, diminished solubility, and resistance to proteolytic digestion. Transgenetic studies argue that PrPc and PrPSc form a complex during PrPScformation; thus, synthetic PrP peptides, which mimic the conformational pluralism of PrP, were mixed with PrPc to determine whether its properties were altered. Peptides encompassing two a-helical domains of PrP when mixed with PrPc produced a complex that displayed many properties of PrPSc. The PrPcpeptide complex formed fibrous aggregates and up to 65% of complexed PrPc sedimented at 100,000 x g for 1 h, whereas PrPc alone did not. These complexes were resistant to pro teolytic digestion and displayed a high /3-sheet content. Un expectedly, the peptide in a /3-sheet conformation did not form the complex, whereas the random coil did. Addition of 2% Sarkosyl disrupted the complex and rendered PrPc sensitive to protease digestion. While the pathogenic AllTV mutation increased the efficacy of complex formation, anti-PrP mono clonal antibody prevented interaction between PrPc and pep tides. Our findings in concert with transgenetic investigations argue that PrPc interacts with PrPSc through a domain that contains the first two putative a-helices. Whether PrPc-peptide complexes possess prion infectivity as determined by bioassays remains to be established.en-USCreative Commons BY-NC-ND 4.0-USArticle