Solid State NMR Structure Analysis of the Antimicrobial Peptide Gramicidin S in Lipid Membranes: Concentration-Dependent Re-alignment and Self-Assembly as a β-Barrel

Antimicrobial peptides can kill bacteria by permeabilizing their cell membrane, as these amphiphilicmolecules interact favourably with lipid bilayers. This mechanism of action is attributed eitherto the formation of a peptide “carpet” on the membrane surface, or to a transmembranepore. However, the structure of such a pore has not yet been resolved under relevant conditions.Gramicidin S is a symmetrical cyclic β-sheet decapeptide, which has been previouslyshown by solid state NMR to lie flat on the membrane surface at low peptide:lipid ratios (≤ 1:80).Using highly sensitive 19F-NMR, supported by 15N-labelling,we found that gramicidin S can flip into an upright transmembrane alignment at hig…