NR AUQY
AU del Pino,P.; Weiss,A.; Bertsch,U.; Renner,C.; Mentler,M.; Grantner,K.; Fiorino,F.; Meyer-Klaucke,W.; Moroder,L.; Kretzschmar,H.A.; Parak,F.G.
TI Molecular Structure of the Cu2+ Binding Sites of Full-Length Human Prion Protein at Different Copper Loading
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Vortrag V-17
PT Konferenz-Vortrag
AB
The cellular prion protein PrPc can bind divalent copper under physiologically relevant conditions and is believed to play a role in the copper metabolism. Several studies have investigated PrPc-derived peptides lacking the structured C-terminal part of the protein to determine the molecular features of the copper binding sites.
Here we present a model for the Cu2+ complex of the octarepeat region in the full-length PrPc.
In our study PrPc-Cu2+-complexes were investigated by EXAFS, EPR, and ENDOR spectroscopy. These results enabled us to build a model for the Cu2+ complex using molecular mechanics computations to select sterically possible and energetically favourable structures. The simulated EPR, ENDOR, and EXAFS spectra of these structures fully agree with the experimental data. Our studies on shorter PrPc-derived peptides demonstrate the importance of sequence length, buffer conditions and amount of copper on the binding motifs. Our obtained model for the Cu2+ complex in the full-length PrPc differs significantly from those previously proposed for shorter peptides in other studies.
AD Pablo del Pino, Andreas Weiss, Christian Renner, Matthias Mentler, Klaus Grantner, Fritz G. Parak, Physik Department E17, Technische Universität München, 85747 Garching; Ferdinando Fiorino, Luis Moroder, Laboratory of Bioorganic Chemistry, Max-Planck-Institut für Biochemie, 82151 Martinsried; Uwe Bertsch, Hans A. Kretzschmar, Zentrum für Neuropathologie und Prionforschung der LMU, 81377 München; Wolfram Meyer-Klaucke, EMBL Outstation Hamburg
SP englisch
PO Deutschland
OR Tagungsband