NR AWQG
AU Watzlawik,J.; Frense,D.; Schulz-Schaeffer,W.J.; Kramer,M.L.
TI Reversible oligomerization of the prion protein under physiological conditions - evidence for 3D domain swapping
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions S-29
PT Konferenz-Poster
AB In prion diseases the alpha-helical prion protein PrPc is converted into the aggregated and infectious isoform PrPsc which is rich in ß-sheet. Using denaturing conditions in vitro the formation of ß-sheet rich oligomers were shown to precede the formation of fibrils. Interestingly, the more unstable ex vivo prion oligomers were demonstrated to be the most infectious particles compared to larger prion aggregates. However, the mechanism of the first steps in the spontaneous oligomerization process under non-denaturing physiological conditions are still elusive. It was proposed that 3D domain swapping play a role in oligomerization and aggregation of proteins. Domain swapping is a mechanism for forming homodimers and higher-order oligomers by the exchange of protein domains where the "swapped" domain can also be an element of secondary structure. For the prion protein 3D domain swapping including disulfide bridge shuffling was suggested as a possible first step in prion protein oligomerization. However, no disulfide-linked oligomers were found in PrPsc. Therefore, we investigated the oligomerization of different prion protein mutants under physiological non-denaturing conditions. To our complete surprise we observed a reversible oligomerization of certain prion mutants with an unusual temperature dependence. It appears that the ß-sheet in PrPc plays an important role in this reversible oligomerization process suggesting that oligomerization is due to domain swapping.
AD J. Watzlawik, W.J. Schulz-Schaeffer, M.L. Kramer: Prion and Dementia Research Unit, Institute of Neuropathology, University of Göttingen, Germany; D. Frense: Institute for Bioprocess and Analytical Measurement Techniques, Heiligenstadt, Germany
SP englisch
PO Italien