NR APAH
AU Weiss,A.; Tavan,P.
TI Structure of Copper(II) complexes with Prion Protein Octapeptide determined by a combination of experiment and theory
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-67
PT Konferenz-Poster
AB
The N-terminal fragments of PrPc can bind Cu(II) ions. Copper binding seems to be essential for the physiological function of PrPc and may be involved in the conformational transition required
for the generation of infectious PrPsc. The overall 3D structure of PrPc has not yet been fully established, since in aqueous solution at low pH and in the absence of bound Cu(II) ions the N-terminus is a random coil. In the presence of Cu(II), however, the N-terminal octapeptide repeat region could assume a well-defined 3D structure. We have developed a novel theoretical approach as to structurally analyze EXAFS, EPR and ENDOR experiments conducted by our
partners [F. Parak et al., TU Muenchen] on copper-peptide complexes. For this purpose we have developed a combined protein-copper force field and, in cooperation with our partners, improved methods for the interpretation of ENDOR data. In so-called annealing simulations, the new molecular mechanics (MM) force field was used for the generation of a set of plausible candidate structures, among which EXAFS and ENDOR data allow a selection of compatible ones. This new approach has beenfirst applied the copper-octapeptide PHGGGWGQ for verification of methods.Applications to octapeptide-repeats are imminent.
AD Andreas Weiss, Paul Tavan, Theoretische Biophysik, BioMolekulare Optik, Sektion Physik, LMU
SP englisch
PO Deutschland