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

• Applicant: Professor Dr. Stephan Schwarzinger
• Subject Area: Structural Biology
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 63588060

• Final Report Year: 2013

Final Report Abstract

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.

Publications

• (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
  (See online at 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
  (See online at https://doi.org/10.1080/073911012010525021)