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Temperature-Dependent Re-alignment of the Short Multifunctional Peptide BP100 in Membranes Revealed by Solid-State NMR Spectroscopy and Molecular Dynamics Simulations |
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| Authors: | Dr Erik Strandberg Dr Parvesh Wadhwani Dr Jochen Bürck Dr Patrick Anders Dr Christian Mink Dr Jonas van den Berg Raffaele A M Ciriello Dr Manuel N Melo Prof?Dr Miguel A R B Castanho Prof?Dr Eduard Bardají Prof?Dr Jakob P Ulmschneider Prof?Dr Anne S Ulrich |
| Affiliation: | 1. Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), POB 3640, 76021 Karlsruhe, Germany;2. Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Contribution: Formal analysis (supporting), ?Investigation (equal);3. Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany Present address: Syngenta Crop Protection AG, 4333 Münchwilen, Switzerland Contribution: Formal analysis (supporting), ?Investigation (equal), Visualization (supporting);4. Instituto de Medicina Molecular Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal;5. LIPPSO, Department of Chemistry, University of Girona, Campus Montilivi, 17071 Girona, Spain Contribution: Formal analysis (equal), ?Investigation (equal), Methodology (equal), Writing - review & editing (supporting);6. Institute of Natural Sciences and School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, 200240 China Contribution: Formal analysis (equal), ?Investigation (equal), Methodology (equal), Visualization (equal), Writing - review & editing (supporting) |
| Abstract: | 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. |
| Keywords: | antimicrobials cationic amphipathic alpha-helices cell-penetrating mechanisms circular dichroism peptide alignment in oriented bilayers side-chain snorkeling |