Abstract
The molecular basis of the infectious, inherited and sporadic forms of prion diseases is best explained by a conformationally dimorphic protein that can exist in distinct normal and disease-causing isoforms. We identified a 55-residue peptide of a mutant prion protein that can be refolded into at least two distinct conformations. When inoculated intracerebrally into the appropriate transgenic mouse host, 20 of 20 mice receiving the β-form of this peptide developed signs of central nervous system dysfunction at ~360 days, with neurohistologic changes that are pathognomonic of Gerstmann-Straussler-Scheinker disease. By contrast, eight of eight mice receiving a non-β-form of the peptide failed to develop any neuropathologic changes more than 600 days after the peptide injections. We conclude that a chemically synthesized peptide refolded into the appropriate conformation can accelerate or possibly initiate prion disease. (C) 2000 Academic Press.
Original language | English (US) |
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Pages (from-to) | 997-1007 |
Number of pages | 11 |
Journal | Journal of Molecular Biology |
Volume | 295 |
Issue number | 4 |
DOIs | |
State | Published - Jan 28 2000 |
Keywords
- Gerstmann-Straussler-Scheinker (GSS) disease
- PrP amyloid plaques
- PrP mutation (P102L)
- Prion protein synthetic peptide
- β-pleated sheet
ASJC Scopus subject areas
- Molecular Biology
- Biophysics
- Structural Biology