NR AOPC
AU Lee,S.; Eisenberg,D.
TI Seeded conversion of recombinant prion protein to a disulfide-bonded oligomer by a reduction-oxidation process
QU Nature Structural Biology 2003 Sep; 10(9): 725-30
PT journal article
AB The infectious form of prion protein, PrPsc, self-propagates by its conversion of the normal, cellular prion protein molecule PrPc to another PrPsc molecule. It has not yet been demonstrated that recombinant prion protein can convert prion protein molecules from PrPc to PrPsc. Here we show that recombinant hamster prion protein is converted to a second form, PrP(RDX), by a redox process in vitro and that this PrP(RDX) form seeds the conversion of other PrPc molecules to the PrP(RDX) form. The converted form shows properties of oligomerization and seeded conversion that are characteristic of PrPsc. We also find that the oligomerization can be reversed in vitro. X-ray fiber diffraction suggests an amyloid-like structure for the oligomerized prion protein. A domain-swapping model involving intermolecular disulfide bonds can account for the stability and coexistence of two molecular forms of prion protein and the capacity of the second form for self-propagation.
MH Animal; Disulfides; Electrophoresis, Polyacrylamide Gel; Endopeptidase K/chemistry; Hamsters; Hydrogen-Ion Concentration; Immunoblotting; Microscopy, Electron; Models, Molecular; Oxidation-Reduction; Plasmids/metabolism; Prions/*chemistry; Protein Binding; Protein Structure, Tertiary; Recombinant Proteins/*chemistry; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; X-Ray Diffraction
AD Howard Hughes Medical Institute, Molecular Biology Institute, UCLA-DOE Institute for Genomics and Proteomics and Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570, USA
SP englisch
PO USA