Abstract
The human prion gene, PRNP, has two allelic forms that encode either a methionine or valine at codon 129. This polymorphism strongly influences the pathogenesis of prion disease. However, the underlying mechanism remains unclear. We compared the conformation between wild-type human prion protein (rPrPC) with either a valine or methionine at position 129, using a panel of monoclonal antibodies that are specific for epitopes along the entire protein. We found that rPrPC(129M) has a more exposed helix 1 region compared to rPrPC(129V). Helix 1 is important in the aggregation process. Accordingly, rPrPC(129M) aggregates at a faster rate and forms more aggregate than rPrPC(129V). In addition, by using a rPrP with a pathogenic mutation of five additional octapeptide repeat insertions, rPrP(129M)/10OR, as "seeds", we showed that rPrP(129M)/10OR promotes the aggregation of rPrPC(129M) more efficiently than rPrPC(129V). These findings provide a possible mechanism underlying the influence of residue 129 on human prion disease.
Original language | English (US) |
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Pages (from-to) | 875-881 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 368 |
Issue number | 4 |
DOIs | |
State | Published - Apr 18 2008 |
Externally published | Yes |
Keywords
- Aggregation
- Epitope
- Polymorphism
- Prion protein
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology