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Updated: May 10, 2026
11:29
Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain
Published on: October 3, 2012
A prion protein epitope selective for the pathologically misfolded conformation
Eustache Paramithiotis1, Marc Pinard, Trebor Lawton
1Caprion Pharmaceuticals Inc., 7150 Alexander-Fleming, St-Laurent, Quebec H4S 2C8, Canada.
Nature Medicine
|June 5, 2003
Summary
Pathological prion protein misfolding exposes tyrosine residues, enabling antibodies targeting the tyrosine-tyrosine-arginine motif to detect disease-associated prion protein. This offers potential for new prion disease diagnostics and therapeutics.
Area of Science:
- Biochemistry
- Neuroscience
- Protein Misfolding Diseases
Background:
- Protein conformational changes are critical in diseases like prion disorders.
- Misfolding often leads to the exposure of previously hidden molecular surfaces.
Purpose of the Study:
- To investigate the molecular changes accompanying prion protein misfolding.
- To develop antibodies that can specifically detect pathological prion protein isoforms.
Main Methods:
- Studied recombinant prion proteins and their beta-sheet structure induction.
- Utilized immunoprecipitation, plate capture immunoassay, and flow cytometry.
- Developed antibodies against the tyrosine-tyrosine-arginine motif.
Main Results:
- Increased solvent accessibility of tyrosine residues correlated with beta-sheet formation in prion proteins.
- Antibodies against the tyrosine-tyrosine-arginine motif specifically recognized the pathological prion protein isoform.
- Antibody binding was saturable and specific, and could be induced in vitro.
Conclusions:
- Conformation-selective exposure of the tyrosine-tyrosine-arginine motif serves as a marker for pathological prion protein.
- This finding has implications for developing novel diagnostics and therapeutics for prion diseases.
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