Temperature‐dependent re‐alignment of the short multifunctional peptide BP100 in membranes revealed by solid‐state NMR spectroscopy and molecular dynamics simulations

© 2022 The Authors. ChemBioChem published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.BP100 is a cationic undecamer peptide with antimicrobial and cell-penetrating activities. The orientation of this amphiphilic α-helix in lipid bilayers was examined under numerous conditions using solid-state 19F, 15N and 2H NMR. At high temperatures in saturated phosphatidylcholine lipids, BP100 lies flat on the membrane surface, as expected. Upon lowering the temperature towards the lipid phase transition, the helix is found to flip into an upright transmembrane orientation. In thin bilayers, this inserted state was stable at low peptide concentration, but thicker membranes required higher peptide concentrations. In the presence of lysolipids, the inserted state prevailed even at high temperature. Molecular dynamics simulations suggest that BP100 monomer insertion can be stabilized by snorkeling lysine side chains. These results demonstrate that even a very short helix like BP100 can span (and thereby penetrate through) a cellular membrane under suitable conditions.We acknowledge financial support for NMR hardware from the German Research Foundation (DFG) project “INST 121384/58-1 FUGG”. This work was also supported financially by the Helmholtz Association Program BIF-TM, by the DFG grant UL127/7-1, by the DAAD “Portugal-Acções Integradas Luso-Alemãs/DAAD-GRICES” grant D/07/13644, and by the Fundação para a Ciência e a Tecnologia grant SFRH/BD/24778/2005. Open Access funding enabled and organized by Projekt DEAL.