NR ATQY
AU Watzlawik,J.; Schulz-Schaeffer,W.J.; Kramer,M.L.
TI Role of helix1 in prion protein aggregation
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Structure of PrP and molecular determinants of infectivity STRCT-14
PT Konferenz-Poster
AB In the process of prion formation in which native alpha-helical PrPc is converted to the infectious and pathological PrPsc a significant part of the prion protein adopts beta-sheet structure. Within the prion protein the region from amino acid 90 to 145 is considered as principal region for conversion to beta-sheet. However, the role of helix1 in this process is unclear. Originally, helix1 was thaught to be converted into beta-sheet since helix2 and helix3 are stabilized by a covalent disulfide bridge. A deletion mutant from amino acid 141 to 177 including the first helix was still converted to a proteinase K resistant form suggesting that helix1 is not essential for PrPsc formation. On the other hand the region about helix1 appears to be essentially involved in the conversion process since PrPsc formation in cell culture was inhibited by antibodies directed against the helix1 region. But recent data demonstrated that the hydrophilic helix1 is rather stable even at lower pH and higher ionic strength pointing against a conversion into beta-sheet. Since experimental data on the role of helix1 in the aggregation process of prion protein were lacking we constructed and expressed mutant prion proteins to investigate their aggregation kinetics, as well as aggregate structure and stability. Our data provide evidence for an aggregation promoting effect of helix1.
AD Jens Watzlawik, Walter J.Schulz-Schaeffer, Michael L.Kramer, Prion and Dementia Resarch Unit, University of Göttingen
SP englisch
PO Deutschland