Membrantransport über elektrostatische 'charge zipper'

• Antragstellerinnen / Antragsteller: Professor Dr. Marcus Elstner; Professorin Dr. Anne Ulrich
• Fachliche Zuordnung: Stoffwechselphysiologie, Biochemie und Genetik der Mikroorganismen ; Bioinformatik und Theoretische Biologie ; Biophysik ; Strukturbiologie ; Theoretische Chemie: Moleküle, Materialien, Oberflächen
• Förderung: Förderung von 2013 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 246585620

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

The project was initially focused on the structure-function analysis of two intriguing peptides in their biologically relevant membrane-bound states: the bacterial toxin TisB, and the human sweat protein dermcidin. We had predicted that both peptides would be assembled as dimers via a novel pattern of electrostatic “charge zippers”. Namely, their highly charged amphiphilic helices should be able to traverse the hydrophobic membrane core by forming a ladder of salt bridges between them. All questions were to be tackled simultaneously by experiment and simulation in a mutually instructive way. The most important outcome is the proof of and structural description of some fundamentally new transmembrane assembly motifs that had not been described before in the literature. These “zippers” are encoded in the protein sequence and drive polar helix-helix interactions in the hydrophobic bilayer.

Projektbezogene Publikationen (Auswahl)

• (2013) “Folding and self-assembly of the TatA translocation pore based on a charge zipper mechanism” Cell, 152, 316–326
  T.H. Walther, C. Gottselig, S.L. Grage, M. Wolf, A.V. Vargiu, M.J. Klein, S. Vollmer, S. Prock, M. Hartmann, S. Afonin, E. Stockwald, H. Heinzmann, O.V. Nolandt, W. Wenzel, P. Ruggerone, A.S. Ulrich
  (Siehe online unter https://doi.org/10.1016/j.cell.2012.12.017)
• (2014) 3D hydrophobic moment vectors as a tool to characterize the surface polarity of amphiphilic peptides, Biophys. J., 106, 2385–2394
  S. Reißer, E. Strandberg, T. Steinbrecher, A.S. Ulrich
  (Siehe online unter https://doi.org/10.1016/j.bpj.2014.04.020)
• (2014) “Controlling biological activity with light: diarylethene-containing cyclic peptidomimetics” Angew. Chem. Int. Ed., 53, 3392–3395
  O. Babii, S. Afonin, M. Berditsch, S. Reißer, P.K. Mykhailiuk, V.S. Kubyshkin, T. Steinbrecher, A.S. Ulrich, I.K. Komarov
  (Siehe online unter https://doi.org/10.1002/anie.201310019)
• (2014) “Transmembrane helix assembly and the role of salt bridges” Curr. Opin. Struct. Biol., 27, 63–68
  T.H. Walther, A.S. Ulrich
  (Siehe online unter https://doi.org/10.1016/j.sbi.2014.05.003)
• (2017) “Structural behavior of the peptaibol harzianin HK VI in a DMPC bilayer - insights from computer simulations” Biophys. J. 112, 2602–2614
  M. Putzu, S. Kara, S. Afonin, S. L. Grage, A. Bordessa, G. Chaume, T. Brigaud, A. S. Ulrich, T. Kubar
  (Siehe online unter https://doi.org/10.1016/j.bpj.2017.05.019)
• (2017) “Structure analysis of the membrane-bound dermcidin-derived peptide SSL-25 from human sweat” BBA Biomembranes, 1859 (2017) 2308–2318
  P. Mühlhäuser, P. Wadhwani, E. Strandberg, J. Bürck, A.S. Ulrich
  (Siehe online unter https://doi.org/10.1016/j.bbamem.2017.09.004)
• (2018) „Best of two worlds? How MD simulations of amphiphilic helical membrane-bound peptides can complement data from oriented solid-state NMR” J. Chem. Theo. Comp. 14, 6002-6014
  S. Reißer, E. Strandberg, T. Steinbrecher, M. Elstner, A.S. Ulrich
  (Siehe online unter https://doi.org/10.1021/acs.jctc.8b00283)
• „Tetrameric Charge-Zipper Assembly of the TisB Peptide in Membranes - Computer Simulation and Experiment” J. Phys. Chem. B 123(8), 1770–1779 (2019)
  V. Schneider, P. Wadhwani, J. Reichert, J. Bürck, M. Elstner, A. S. Ulrich, T. Kubař
  (Siehe online unter https://doi.org/10.1021/acs.jpcb.8b12087)