Advertisement

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

  • Sergii Afonin
  • Ulrich H.N. Dürr
  • Parvesh Wadhwani
  • Jesus Salgado
  • Anne S. UlrichEmail author
Chapter
Part of the Topics in Current Chemistry book series (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.

Amphiphilic peptide–lipid interactions Cyclic β-sheet structure Peptide re-alignment and self-assembly Pore formation Solid state 19F-NMR and 15N-NMR  

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hancock RE (2001) Lancet Infect Dis 1:156 CrossRefGoogle Scholar
  2. 2.
    Zasloff M (2002) Nature 415:389 CrossRefGoogle Scholar
  3. 3.
    Hull SE, Karlsson R, Main P, Woolfson MM, Dodoson EJ (1978) Nature 275:206 CrossRefGoogle Scholar
  4. 4.
    Xu Y, Sugár IP, Krishna R (1995) J Biomol NMR 5:37 CrossRefGoogle Scholar
  5. 5.
    McElhaney RN, Prenner EJ (1999) Biochim Biophys Acta 1462:1 CrossRefGoogle Scholar
  6. 6.
    Wu M, Maier E, Benz R, Hancock RE (1999) Biochemistry 38:7235 CrossRefGoogle Scholar
  7. 7.
    Bechinger B, Sizun C (2003) Concepts Magn Reson 18A:130 CrossRefGoogle Scholar
  8. 8.
    Strandberg E, Ulrich AS (2004) Concepts Magn Reson 23A:89 CrossRefGoogle Scholar
  9. 9.
    Opella SJ, Marassi FM (2004) Chem Rev 104:3587 CrossRefGoogle Scholar
  10. 10.
    Henzler-Wildman KA, Lee DK, Ramamoorthy A (2003) Biochemistry 42:6545 CrossRefGoogle Scholar
  11. 11.
    Grage SL, Ulrich AS (1999) J Magn Reson 138:98 CrossRefGoogle Scholar
  12. 12.
    Grage SL, Ulrich AS (2000) J Magn Reson 146:81 CrossRefGoogle Scholar
  13. 13.
    Toke O, O’Connor RD, Weldeghiorghis TK, Maloy WL, Glaser RW, Ulrich AS, Schaefer J (2004) Biophys J 87:675 CrossRefGoogle Scholar
  14. 14.
    Crocker E, Patel AB, Eilers M, Jayaraman S, Getmanova E, Reeves PJ, Ziliox M, Khorana HG, Sheves M, Smith SO (2004) J Biomol NMR 29:11 CrossRefGoogle Scholar
  15. 15.
    Porcelli F, Buck B, Lee DK, Hallock KJ, Ramamoorthy A, Veglia G (2004) J Biol Chem 279:45815 CrossRefGoogle Scholar
  16. 16.
    Ulrich AS (2000) High resolution solid state NMR, 1H, 19F. In: Lindon J, Tranter G, Holmes J (eds) Encyclopedia of spectroscopy and spectrometry. Academic, London, p 813 Google Scholar
  17. 17.
    Salgado J, Grage SL, Kondejewski LH, Hodges RS, McElhaney RN, Ulrich AS (2001) J Biomol NMR 21:191 CrossRefGoogle Scholar
  18. 18.
    Afonin S, Dürr UHN, Glaser RW, Ulrich AS (2004) Magn Reson Chem 42:195 CrossRefGoogle Scholar
  19. 19.
    Glaser RW, Sachse C, Dürr UHN, Wadhwani P, Ulrich AS (2004) J Magn Reson 168:153 CrossRefGoogle Scholar
  20. 20.
    Getmanova E, Patel AB, Klein-Seetharaman J, Loewen MC, Reeves PJ, Friedman N, Sheves M, Smith SO, Khorana HG (2004) Biochemistry 43:1126 CrossRefGoogle Scholar
  21. 21.
    Glaser RW, Sachse C, Durr UH, Wadhwani P, Afonin S, Strandberg E, Ulrich AS (2005) Biophys J 88:3392 CrossRefGoogle Scholar
  22. 22.
    Ulrich AS (2005) Prog NMR Spectr 46:1 CrossRefGoogle Scholar
  23. 23.
    Ulrich AS, Wadhwani P, Dürr UHN, Afonin S, Glaser RW, Strandberg E, Tremouilhac P, Sachse C, Berditchevskaia M, Grage S (2006) Solid-state 19F-nuclear magnetic resonance analysis of membrane-active peptides. In: Ramamoorthy A (ed) NMR spectroscopy of biological solids. Taylor & Francis, London, p 215 Google Scholar
  24. 24.
    Ulrich AS (2007) Solid state 19F-NMR analysis of oriented biomembranes. In: Webb GA (ed) Modern magnetic resonance. Springer, p 257 Google Scholar
  25. 25.
    Glaser RW, Ulrich AS (2003) J Magn Reson 164:104 CrossRefGoogle Scholar
  26. 26.
    Huang HW, Chen FY, Lee MT (2004) Phys Rev Lett 92:198304 CrossRefGoogle Scholar
  27. 27.
    Afonin S, Glaser RW, Berditchevskaia M, Wadhwani P, Gührs KH, Möllmann U, Perner A, Ulrich AS (2003) ChemBioChem 4:1151 CrossRefGoogle Scholar
  28. 28.
    Mikhailiuk PK, Afonin S, Chernega AN, Rusanov EB, Platonov M, Dubinia G, Ulrich AS, Komarov IV (2006) Angew Chem Int Ed Engl 45:5659 CrossRefGoogle Scholar
  29. 29.
    Wadhwani P, Afonin S, Ieronimo M, Buerck J, Ulrich AS (2006) J Org Chem 71:55 CrossRefGoogle Scholar
  30. 30.
    Massiot D, Fayon F, Capron M, King I, Le Calve S, Alonso B, Durand J-O, Bujoli B, Gan Z, Hoatson G (2002) Magn Res Chem 40:70 CrossRefGoogle Scholar
  31. 31.
    Strandberg E, Wadhwani P, Tremouilhac P, Dürr UHN, Ulrich AS (2006) Biophys J 90:1676 CrossRefGoogle Scholar
  32. 32.
    Afonin S (2004) Structural studies on membrane-active peptides in lipid bilayers by solid state 19F-NMR. PhD thesis. Institute of Molecular Biology. Friedrich-Schiller-Universität, Jena, p 98 Google Scholar
  33. 33.
    Dürr UHN (2005) Solid-state 19F-NMR studies on fluorine-labeled model compounds and biomolecules. PhD thesis. Institute of Organic Chemistry. Universität Karlsruhe (TH), Karlsruhe, p 163 Google Scholar
  34. 34.
    Steiner H, Andreu D, Merrifield RB (1988) Biochim Biophys Acta 939:260 CrossRefGoogle Scholar
  35. 35.
    Blazyk J, Wiegand R, Klein J, Hammer J, Epand RM, Epand RF, Maloy WL, Kari UP (2001) J Biol Chem 276:27899 CrossRefGoogle Scholar
  36. 36.
    Hallock KJ, Lee DK, Ramamoorthy A (2003) Biophys J 84:3052 CrossRefGoogle Scholar
  37. 37.
    Mani R, Waring AJ, Lehrer RI, Hong M (2005) Biochim Biophys Acta 1716:11 CrossRefGoogle Scholar
  38. 38.
    Mani R, Buffy JJ, Waring AJ, Lehrer RI, Hong M (2004) Biochemistry 43:13839 CrossRefGoogle Scholar
  39. 39.
    Grage SL, Wang J, Cross TA, Ulrich AS (2002) Biophys J 83:3336 CrossRefGoogle Scholar
  40. 40.
    Möllhoff M, Sternberg U (2001) J Mol Model 7:90 Google Scholar
  41. 41.
    Yamaguchi S, Huster D, Waring A, Lehrer RI, Kearney W, Tack BF, Hong M (2001) Biophys J 81:2203 CrossRefGoogle Scholar
  42. 42.
    Wimley WC (2003) Curr Opin Struct Biol 13:404 CrossRefGoogle Scholar
  43. 43.
    Montoya M, Gouaux E (2003) Biochim Biophys Acta 1609:19 CrossRefGoogle Scholar
  44. 44.
    Grotenbreg GM, Timmer MS, Llamas-Saiz AL, Verdoes M, van der Marel GA, van Raaij MJ, Overkleeft HS, Overhand M (2004) J Am Chem Soc 126:3444 CrossRefGoogle Scholar
  45. 45.
    Maxfield FR (2002) Curr Opin Cell Biol 14:483 CrossRefGoogle Scholar
  46. 46.
    McInnes C, Kondejewski LH, Hodges RS, Sykes BD (2000) J Biol Chem 275:14287 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Sergii Afonin
    • 1
  • Ulrich H.N. Dürr
    • 2
  • Parvesh Wadhwani
    • 1
  • Jesus Salgado
    • 3
  • Anne S. Ulrich
    • 1
    • 4
    Email author
  1. 1.Karlsruhe Institute of Technology (KIT), Institut für Biologische GrenzflächenKarlsruheGermany
  2. 2.Max Planck Institut für Biophysikalische Chemie, Department of NMR-Based StructuralBiologyGöttingenGermany
  3. 3.Instituto de Sciencia MolecularUniversitat de ValènciaPaterna (Valencia)Spain
  4. 4.Karlsruhe Institute of Technology (KIT), Institut für Organische ChemieKarlsruheGermany

Personalised recommendations