Tetrameric Charge-Zipper Assembly of the TisB Peptide in MembranesComputer Simulation and Experiment

• Published in: The journal of physical chemistry. B 2019-02, Vol.123 (8), p.1770-1779
• Main Authors: Schneider, Violetta, Wadhwani, Parvesh, Reichert, Johannes, Bürck, Jochen, Elstner, Marcus, Ulrich, Anne S, Kubař, Tomáš
• Format: Article
• Language: English
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/acs.jpcb.8b12087

TisB is a short amphiphilic α-helical peptide from Escherichia coli that induces a breakdown of the pH gradient across the inner membrane when the bacteria are under stress and require to form persister cells to turn into a biofilm. A computational–experimental approach combining all-atom and coarse-grained molecular dynamics simulation with circular dichroism spectroscopy and gel electrophoresis was used to reveal its structure and oligomeric assembly in a phospholipid bilayer. TisB is found to be inserted upright in the membrane as a tetrameric bundle with a left-handed sense of supercoiling, best described as an antiparallel dimer-of-dimers. The tetramer is stabilized by means of a regular but dynamically interchanging pattern of salt bridges and hydrogen bonds, in accordance with the recently proposed “charge-zipper” motif.