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Strain-dependent differences in beta-sheet conformations of abnormal prion protein
B Caughey1, G J Raymond, R A Bessen
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA. byron_caughey@nih.gov
The Journal of Biological Chemistry
|November 21, 1998
Summary
Transmissible spongiform encephalopathies (TSEs) strain diversity may stem from prion protein (PrP-res) conformation variations. This study found distinct PrP-res structures in hamster TSE strains, supporting strain-specific conformer propagation.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases.
- Strain diversity in TSEs is hypothesized to arise from variations in the abnormal prion protein (PrP-res) conformation.
Purpose of the Study:
- To investigate if three TSE strains (hyper, drowsy, 263K) induce distinct PrP-res conformations in hamsters.
- To correlate PrP-res conformation with TSE strain characteristics.
Main Methods:
- Limited proteinase K (PK) digestion of PrP-res from infected hamster brains.
- Infrared spectroscopy to analyze PrP-res secondary structure.
- SDS-polyacrylamide gel electrophoresis for initial PrP-res profiling.
Main Results:
- PrP-res from DY strain showed distinct PK digestion fragmentation compared to HY and 263K strains.
- Infrared spectroscopy revealed unique beta-sheet structural differences in DY PrP-res compared to HY and 263K strains.
- HY and 263K PrP-res shared similar spectral features, distinct from DY PrP-res.
Conclusions:
- The study provides evidence for strain-specific PrP-res conformations in TSEs.
- Distinct PrP-res structures correlate with different TSE disease phenotypes.
- These findings support the self-propagation model of strain-specific prion conformers.