Prion protein (PrP) synthetic peptides induce cellular PrP to acquire properties of the scrapie isoform
| dc.contributor.author | Kaneko, K. | |
| dc.contributor.author | Peretz, David | |
| dc.contributor.author | Pan, K. K. | |
| dc.contributor.author | Blochberger, Thomas C. | |
| dc.contributor.author | Wille, H. | |
| dc.contributor.author | Gabizon, R. | |
| dc.contributor.author | Griffith, O. H. | |
| dc.contributor.author | Cohen, F. E. | |
| dc.contributor.author | Baldwin, Michael A. | |
| dc.contributor.author | Prusiner, Stanley B. | |
| dc.date.accessioned | 2016-06-03T18:54:38Z | |
| dc.date.available | 2016-06-03T18:54:38Z | |
| dc.date.issued | 1995-11 | |
| dc.description | 5 pages | en_US |
| dc.description.abstract | Conversion 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_US |
| dc.identifier.citation | Kaneko, 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. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1794/19934 | |
| dc.language.iso | en_US | en_US |
| dc.publisher | Proceedings of the National Academy of Sciences | en_US |
| dc.rights | Creative Commons BY-NC-ND 4.0-US | en_US |
| dc.title | Prion protein (PrP) synthetic peptides induce cellular PrP to acquire properties of the scrapie isoform | en_US |
| dc.type | Article | en_US |