Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1995 Nov 21;92(24):11160-4.
doi: 10.1073/pnas.92.24.11160.

Prion protein (PrP) synthetic peptides induce cellular PrP to acquire properties of the scrapie isoform

K Kaneko  1 , D Peretz, K M Pan, T C Blochberger, H Wille, R Gabizon, O H Griffith, F E Cohen, M A Baldwin, S B Prusiner
Affiliations

Prion protein (PrP) synthetic peptides induce cellular PrP to acquire properties of the scrapie isoform

K Kaneko et al. Proc Natl Acad Sci U S A. .

Abstract

Conversion of the cellular isoform of prion protein (PrPC) into the scrapie isoform (PrPSc) involves an increase in the beta-sheet content, diminished solubility, and resistance to proteolytic digestion. Transgenetic studies argue that PrPC and PrPSc form a complex during PrPSc formation; 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 alpha-helical domains of PrP when mixed with PrPC produced a complex that displayed many properties of PrPSc. The PrPC-peptide 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 proteolytic digestion and displayed a high beta-sheet content. Unexpectedly, the peptide in a beta-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 A117V mutation increased the efficacy of complex formation, anti-PrP monoclonal antibody prevented interaction between PrPC and peptides. Our findings in concert with transgenetic investigations argue that PrPC interacts with PrPSc through a domain that contains the first two putative alpha-helices. Whether PrPC-peptide complexes possess prion infectivity as determined by bioassays remains to be established.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Immunol. 1991 Nov 15;147(10):3568-74 - PubMed
    1. Biochemistry. 1991 Aug 6;30(31):7672-80 - PubMed
    1. J Virol. 1992 Oct;66(10):6155-63 - PubMed
    1. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10940-4 - PubMed
    1. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):1-5 - PubMed

Publication types