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Formation of native prions from minimal components in vitro

Open access
Deleault, Nathan R., Harris, Brent T., Rees, Judy R., Supattapone, Surachai·2007·Proceedings of the National Academy of Sciences

Abstract

The conformational change of a host protein, PrP C , into a disease-associated isoform, PrP Sc , appears to play a critical role in the pathogenesis of prion diseases such as Creutzfeldt–Jakob disease and scrapie. However, the fundamental mechanism by which infectious prions are produced in neurons remains unknown. To investigate the mechanism of prion formation biochemically, we conducted a series of experiments using the protein misfolding cyclic amplification (PMCA) technique with a preparation containing only native PrP C and copurified lipid molecules. These experiments showed that successful PMCA propagation of PrP Sc molecules in a purified system requires accessory polyanion molecules. In addition, we found that PrP Sc molecules could be formed de novo from these defined components in the absence of preexisting prions. Inoculation of samples containing either prion-seeded or spontaneously generated PrP Sc molecules into hamsters caused scrapie, which was transmissible on second passage. These results show that prions able to infect wild-type hamsters can be formed from a minimal set of components including native PrP C molecules, copurified lipid molecules, and a synthetic polyanion.

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Metadata

Authors
Deleault, N. R., Harris, B. T., Rees, J. R., & Supattapone, S.
Venue
Proceedings of the National Academy of Sciences
Published
2007-06-05
Volume
104
Issue
23
Pages
9741-9746
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2067540111
Cited by
631
References
49
FWCI
20.95
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Formation of native prions from minimal components in vitro. https://app.cochat.ai/papers/10.1073/pnas.0702662104
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Deleault, N. R., Harris, B. T., Rees, J. R., & Supattapone, S. (2007). Formation of native prions from minimal components in vitro. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0702662104

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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