The importance of the disulfide bond in prion protein conversion.

Abstract

The conversion of normal, protease sensitive prion protein (PrP-sen) to the abnormal protease-resistant form (PrP-res) is of central importance in the pathogenesis of scrapie and other transmissible spongiform encephalopathies. In the present study, the effects of reduction of the disulfide bond on the PrP-sen to PrP-res conversion in a cell-free system were examined. The addition of the disulfide reducing agent dithiothreitol inhibited the cell-free conversion reaction with an IC50 of 2-2.5 mM. Separate pretreatment of either PrP-sen or PrP-res with dithiothreitol and an alkylating agent also inhibited the conversion reaction. Results of this study show that preservation of the disulfide bond is important in the conversion of PrP-sen to PrP-res.

• Authors: L M Herrmann, B Caughey
• Journal: Neuroreport (Neuroreport) Vol. 9 Issue 11 Pg. 2457-61 (Aug 03 1998) ISSN: 0959-4965 [Print] England
• PMID: 9721914 (Publication Type: Journal Article)

Chemical References

• Disulfides
• Prions
• Reducing Agents
• Sulfhydryl Reagents
• Dithionite
• Endopeptidase K
• Ascorbic Acid
• Dithiothreitol

Topics

• Alkylation
• Animals
• Ascorbic Acid (chemistry)
• Autoradiography
• Cell-Free System
• Cricetinae
• Disulfides (chemistry)
• Dithionite (chemistry)
• Dithiothreitol (chemistry)
• Endopeptidase K (chemistry)
• Mesocricetus
• Prions (chemistry)
• Protein Conformation
• Reducing Agents (chemistry)
• Sulfhydryl Reagents (chemistry)