NR AFIT
AU Herrmann,L.M.; Caughey,B.W.
TI The importance of the disulfide bond in prion protein conversion
QU Neuroreport 1998 Aug 3; 9(11): 2457-61
PT journal article
AB The conversion of normal, protease sensitive prion protein (PrP-sen) to the abnormal protease-resistant form (PrPres) 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 PrPres 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 PrPres 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 PrPres.
MH Alkylation; Animal; Ascorbic Acid/chemistry; Autoradiography; Cell-Free System; Disulfides/chemistry; Dithionite/chemistry; Dithiothreitol/chemistry; Endopeptidase K/chemistry; Hamsters; Mesocricetus; Prions/*chemistry; Protein Conformation; Reducing Agents/chemistry; Sulfhydryl Reagents/chemistry
AD National Institute of Health, National Institute of Allergy and Infectious Disease, Rocky Mountain Laboratories, Laboratory of Persistent Viral Diseases, Hamilton, MT 59840, USA
SP englisch
PO England