NR AURT
AU Weiss,A.; Parak,F.G.
TI Structural Instability of the Prion Protein upon Membrane Mimics Probed by Molecular Dynamics Simulations
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Poster: Struktur und molekulare Mechanismen MOL-17
PT Konferenz-Poster
AB
Prions are the causative agents of a class of disease known as transmissible spongiform encephalopathies (TSE). They are composed largely, if not entirely, of pathogenic conformational misfoldings, called PrPsc, of the cellular prion protein PrPc. In spite of many data available from in vitro conversion experiments of PrPc to its isoform PrPsc only little is known about the primary events inducing the conformational change.
Molecular dynamics simulations of PrPc using conditions known to induce a conversion to PrPsc in "in vitro" experiments were used to investigate the structural instabilities and possibly the early stages of PrP misfolding.
DPC Micelles Induce Structuring of Prion Protein Copper Binding Site
The NMR analysis of membrane bound PrPc showed a largely a-helical C-terminus and a flexible N-terminus without well-defined secondary structure. This unstructured part of the protein contains four successive octapeptide repeats, which were shown to bind up to four Cu2+ ions. To mimic the location of the protein on the cell membrane and to analyze possible structuring effects of the lipid/water interface, the conformational preferences of a single octapeptide repeat and the tetraoctapeptide were simulated in aqueous and DPC micellar solution as membrane mimetic.
AD Andreas Weiss, Fritz G. Parak, Physik-Department E17, Technische Universität München, 85747 Garching, Germany
SP englisch
PO Deutschland
OR Tagungsband