Transport across membranes via electrostatic 'charge zippers'

• Applicants: Professor Dr. Marcus Elstner; Professorin Dr. Anne Ulrich
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Bioinformatics and Theoretical Biology ; Biophysics ; Structural Biology ; Theoretical Chemistry: Molecules, Materials, Surfaces
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246585620

• Final Report Year: 2019

Final Report Abstract

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.

Publications

• (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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at https://doi.org/10.1021/acs.jpcb.8b12087)