Karlsruhe Institute of Technology - KIT
Our research is focused on molecular tools and machineries that are involved in transport across biomembranes. This includes direct bilayer permeabilization by antimicrobial, cell-penetrating and fusogenic peptides, but also specific ion transport by biofilm-inducing peptides and ion channels, as well as highly orchestrated events such as protein translocation and tyrosine-kinase receptor signaling. Solid-state NMR spectroscopy with selective 19F-labels (and/or amino acid type selective 15N-labels) in aligned samples offers the advantage of studying membrane-bound peptides and transmembrane protein segments in a highly sensitive manner under quasi-native conditions, i.e. embedded in any desired lipid composition and at ambient temperature. This way, dynamical properties and structural re-arrangements can be addressed in a biologically relevant environment, and the lipid molecules and morphological changes of the bilayer can be observed at the same time. Our methodological spectrum is rounded off by other biophysical methods, such as circular dichroism (at our ANKA synchrotron-beamline), FRET, DSC, MD simulations (in cooperation), etc., besides the appropriate (micro)biological and functional assays.
Publications:
Walther, T.H., A.S. Ulrich Transmembrane helix assembly and the role of salt bridges, Curr. Opinin. Struct. Biol. (2014) 27, 63–68 PubMed
Babii, O., S. Afonin, M. Berditsch, S. Reißer, P.K. Mykhailiuk, V.S. Kubyshkin, T. Steinbrecher, A.S. Ulrich*, I.K. Komarov* Controlling biological activity with light: diarylethene-containing cyclic peptidomimetic, Angew. Chem. Int. Ed. (2014) 53, 3392–3395 PubMed
Walther, T.H., 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 Folding and self-assembly of the TatA translocation pore based on a charge zipper mechanism, Cell (2013) 152, 316–326 PubMed
Tkachenko, A.N., D.S. Radchenko, P.K. Mykhailiuk, S. Afonin, A.S. Ulrich*, I.V. Komarov* Design, synthesis, and application of a trifluoromethylated phenylalanine analogue as a label to study peptides by solid-state 19F NMR spectroscopy, Angew. Chem. Int. Ed., 52, 6504-6507 PubMed
Strandberg, E., J. Zerweck, P. Wadhwani, A.S. Ulrich Synergistic insertion of antimicrobial magainin-family peptides depends on the lipid spontaneous curvature, Biophys. J. (2013) 104, L9–L11 PubMed
Muhle-Goll, C., S. Hoffmann, S. Afonin, S.L. Grage, A.A. Polyanski, D. Windisch, M. Zeitler, J. Bürck, A.S. Ulrich Hydrophobic matching controls the tilt and stability of the dimeric platelet-derived growth factor receptor (PDGFR)β transmembrane segment, J. Biol. Chem. (2012) 287, 26178-26186 PubMed
Wadhwani, P., E. Strandberg, N. Heidenreich, J. Bürck, S. Fanghänel, A.S. Ulrich Self-assembly of flexible strands into immobile amyloid-like -sheets in membranes as revealed by solid-state 19F-NMR, J. Am. Chem. Soc. (2012) 134: 6512–6515 PubMed
Strandberg E., D. Tiltak, S. Ehni, P. Wadhwani, A.S. Ulrich Lipid shape is a key factor for membrane interactions of amphipathic helical peptides, Biochim. Biophys. Acta - Biomembranes (2012) 1818: 1764–1776 PubMed
Walther T.H., S.L. Grage, N. Roth, A.S. Ulrich Membrane alignment of the pore-forming component TatA(d) of the twin-arginine translocase from B. subtilis resolved by solid-state NMR spectroscopy, J. Am. Chem. Soc. 132, 15945-15956
10. Ieronimo, M., S. Afonin, K. Koch, M. Berditsch, P. Wadhwani, A.S. Ulrich 19F-NMR analysis of the antimicrobial peptide PGLa bound to native cell membranes from bacterial protoplasts and human erythrocytes, J. Am Chem. Soc. (2010) 132: 8822-8824 PubMed
