Struktur und Dynamik von Konformeren des Prionproteins im Verlauf der pathogenen Konformationsänderung PrPC -> PrPSc

• Antragsteller: Professor Dr. Stephan Schwarzinger
• Fachliche Zuordnung: Strukturbiologie
• Förderung: Förderung von 2008 bis 2012
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 63588060

• Erstellungsjahr: 2013

Zusammenfassung der Projektergebnisse

In summary, we have been able to develop a suite of tools a) relying on paramagnetic line broadening and b) using a combination of the NMR-chemical shift in combination with molecular modeling to study the conformational rearrangement of PrP. Despite unexpected difficulties in the generation of selectively spin-labeled prion protein variants we have prepared selectively as well as non-selectively spin-labeled prion protein variants and have recorded NMR spectra at ambient as well as high pressure. Finally, it should be mentioned that it would not have been possible to overcome the difficulties in generating covalently spin labeled prion protein variants without the technical assistant granted for the project, as large amounts of many variants of 15N-labeled protein were required to produce NMR samples.

Projektbezogene Publikationen (Auswahl)

• (2009): SEMPRE: spectral editing mediated by paramagnetic relaxation enhancement, J. Am Chem. Soc. 131, 18016‐18017
  R. Kellner, C. Mangels, K. Schweimer, S.J. Prasch, P.R. Weigelmeier, P. Rösch, S. Schwarzinger
  
• (2010): Formation of transient dimers of a retroviral protease. Biochem. J. 427, 197‐203
  M. Hartl, K. Schweimer, M.H. Reger, S. Schwarzinger, J. Bodem, P. Rösch, B.M. Wöhrl
  
• (2010): The therapeutically anti-prion active antibody-fragment scFv-W226: paramagnetic relaxation enhanced NMR spectroscopy aided structure elucidation of the paratope-epitope interface. J. Biomol. Stuct. Dyn. 28, 13-22
  C. Mangels, R. Kellner, J. Einsiedel, P.R. Weiglmeier, P. Rösch, P. Gmeiner, S. Schwarzinger
  
• (2012): Energy Landscape of the Prion Protein Helix H1 Probed by Metadynamics and NMR. Biophys. J. 102, 158-67
  C. Camillioni, D. Schaal, K. Schweimer, S. Schwarzinger, A. De Simone
  (Siehe online unter https://doi.org/10.1016/j.bpj.2011.12.003)
• (2012): Fast Mapping of biomolecular interfaces by random spin labeling (RSL). J. Biomol. Struct. Dyn. 29, 793-8
  M.J. Hartl, B.M. Burmann, S.J. Prasch, C. Mangels, R. Kellner, K. Schweimer, C. Schwarzinger, P. Rösch, S. Schwarzinger
  (Siehe online unter https://doi.org/10.1080/073911012010525021)