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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

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Bioactive Conformation II

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 273))

Abstract

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 high peptide:lipidratios (≥ 1:40). Orientational NMR constraints suggest that the peptide may self-assembleas an oligomeric β-barrel pore, which is stabilized by intermolecular hydrogen bonds. Comparisonof different model membranes shows that the observed re-alignment is favoured in thin bilayers withshort-chain lipids, especially near the chain melting temperature, whereas long-chain lipids suppresspore formation. Based on the oligomeric structural model and the conditions of pore formation, guidelinesmay now be derived for rationally designing peptide analogues as antibiotics with improved selectivityand reduced side effects.

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Authors and Affiliations

  1. Karlsruhe Institute of Technology (KIT), Institut für Biologische Grenzflächen, PO Box 3640, 76021, Karlsruhe, Germany

    Sergii Afonin, Parvesh Wadhwani & Anne S. Ulrich

  2. Max Planck Institut für Biophysikalische Chemie, Department of NMR-Based StructuralBiology, Fassberg 11, 37077, Göttingen, Germany

    Ulrich H.N. Dürr

  3. Instituto de Sciencia Molecular, Universitat de València, Poligono la Coma s/n, 46980, Paterna (Valencia), Spain

    Jesus Salgado

  4. Karlsruhe Institute of Technology (KIT), Institut für Organische Chemie, Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany

    Anne S. Ulrich

Authors
  1. Sergii Afonin
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  2. Ulrich H.N. Dürr
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  3. Parvesh Wadhwani
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  4. Jesus Salgado
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  5. Anne S. Ulrich
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Corresponding author

Correspondence to Anne S. Ulrich .

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Thomas Peters

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© 2008 Springer-Verlag Berlin Heidelberg

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Afonin, S., Dürr, U.H., Wadhwani, P., Salgado, J., Ulrich, A.S. (2008). 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. In: Peters, T. (eds) Bioactive Conformation II. Topics in Current Chemistry, vol 273. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2007_20

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