On the Role of NMR Spectroscopy for Characterization of Antimicrobial Peptides

  • Fernando Porcelli
  • Ayyalusamy Ramamoorthy
  • George Barany
  • Gianluigi Veglia
Part of the Methods in Molecular Biology book series (MIMB, volume 1063)


Antimicrobial peptides (AMPs) provide a primordial source of immunity, conferring upon eukaryotic cells resistance against bacteria, protozoa, and viruses. Despite a few examples of anionic peptides, AMPs are usually relatively short positively charged polypeptides, consisting of a dozen to about a hundred amino acids, and exhibiting amphipathic character. Despite significant differences in their primary and secondary structures, all AMPs discovered to date share the ability to interact with cellular membranes, thereby affecting bilayer stability, disrupting membrane organization, and/or forming well-defined pores. AMPs selectively target infectious agents without being susceptible to any of the common pathways by which these acquire resistance, thereby making AMPs prime candidates to provide therapeutic alternatives to conventional drugs. However, the mechanisms of AMP actions are still a matter of intense debate. The structure–function paradigm suggests that a better understanding of how AMPs elicit their biological functions could result from atomic resolution studies of peptide–lipid interactions. In contrast, more strict thermodynamic views preclude any roles for three-dimensional structures. Indeed, the design of selective AMPs based solely on structural parameters has been challenging. In this chapter, we will focus on selected AMPs for which studies on the corresponding AMP–lipid interactions have helped reach an understanding of how AMP effects are mediated. We will emphasize the roles of both liquid- and solid-state NMR spectroscopy for elucidating the mechanisms of action of AMPs.

Key words

Antimicrobial peptides Solution NMR Solid-state NMR Lipid membranes 



This work is partially supported by the National Institute of Health (GM 64742 to G.V.).


  1. 1.
    Bommarius B, Kalman D (2009) Antimicrobial and host defense peptides for therapeutic use against multidrug-resistant pathogens: new hope on the horizon. IDrugs 12:376–380PubMedGoogle Scholar
  2. 2.
    Bragonzi A (2010) Fighting back: peptidomimetics as a new weapon in the battle against antibiotic resistance. Sci Transl Med 2:21ps29CrossRefGoogle Scholar
  3. 3.
    Giamarellou H, Poulakou G (2009) Multidrug-resistant Gram-negative infections: what are the treatment options? Drugs 69:1879–1901PubMedCrossRefGoogle Scholar
  4. 4.
    Gryllos I, Tran-Winkler HJ, Cheng MF, Chung H, Bolcome R 3rd, Lu W, Lehrer RI, Wessels MR (2008) Induction of group A Streptococcus virulence by a human antimicrobial peptide. Proc Natl Acad Sci USA 105:16755–16760PubMedCrossRefGoogle Scholar
  5. 5.
    Ho J, Tambyah PA, Paterson DL (2010) Multiresistant Gram-negative infections: a global perspective. Curr Opin Infect Dis 23:546–553PubMedCrossRefGoogle Scholar
  6. 6.
    Paterson DL (2006) Clinical experience with recently approved antibiotics. Curr Opin Pharmacol 6:486–490PubMedCrossRefGoogle Scholar
  7. 7.
    Cornaglia G, Rossolini GM (2009) Forthcoming therapeutic perspectives for infections due to multidrug-resistant Gram-positive pathogens. Clin Microbiol Infect 15:218–223PubMedCrossRefGoogle Scholar
  8. 8.
    Wu G, Li X, Fan X, Wu H, Wang S, Shen Z, Xi T (2011) The activity of antimicrobial peptide S-thanatin is independent on multidrug-resistant spectrum of bacteria. Peptides 32:1139–1145PubMedCrossRefGoogle Scholar
  9. 9.
    Marr AK, Gooderham WJ, Hancock RE (2006) Antibacterial peptides for therapeutic use: obstacles and realistic outlook. Curr Opin Pharmacol 6:468–472PubMedCrossRefGoogle Scholar
  10. 10.
    Steiner H, Hultmark D, Engstrom A, Bennich H, Boman HG (1981) Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292:246–248PubMedCrossRefGoogle Scholar
  11. 11.
    Wiesner J, Vilcinskas A (2010) Antimicrobial peptides: the ancient arm of the human immune system. Virulence 1:440–464PubMedCrossRefGoogle Scholar
  12. 12.
    Zasloff M (2007) Antimicrobial peptides, innate immunity, and the normally sterile urinary tract. J Am Soc Nephrol 18:2810–2816PubMedCrossRefGoogle Scholar
  13. 13.
    Jenssen H, Hamill P, Hancock RE (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19:491–511PubMedCrossRefGoogle Scholar
  14. 14.
    Berridge NJ (1949) Preparation of the antibiotic nisin. Biochem J 45:486–493PubMedGoogle Scholar
  15. 15.
    Mattick AT, Hirsch A (1947) Further observations on an inhibitory substance (nisin) from lactic streptococci. Lancet 2:5–8PubMedCrossRefGoogle Scholar
  16. 16.
    Ambatipudi K, Joss J, Raftery M, Deane E (2008) A proteomic approach to analysis of antimicrobial activity in marsupial pouch secretions. Dev Comp Immunol 32:108–120PubMedCrossRefGoogle Scholar
  17. 17.
    Schittek B, Paulmann M, Senyurek I, Steffen H (2008) The role of antimicrobial peptides in human skin and in skin infectious diseases. Infect Disord Drug Targets 8:135–143PubMedCrossRefGoogle Scholar
  18. 18.
    Steffen H, Rieg S, Wiedemann I, Kalbacher H, Deeg M, Sahl HG, Peschel A, Gotz F, Garbe C, Schittek B (2006) Naturally processed dermcidin-derived peptides do not permeabilize bacterial membranes and kill microorganisms irrespective of their charge. Antimicrob Agents Chemother 50:2608–2620PubMedCrossRefGoogle Scholar
  19. 19.
    Hata TR, Gallo RL (2008) Antimicrobial peptides, skin infections, and atopic dermatitis. Semin Cutan Med Surg 27:144–150PubMedCrossRefGoogle Scholar
  20. 20.
    Lai Y, Gallo RL (2009) AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol 30:131–141PubMedCrossRefGoogle Scholar
  21. 21.
    Menousek J, Mishra B, Hanke ML, Heim CE, Kielian T, Wang G (2012) Database screening and in vivo efficacy of antimicrobial peptides against methicillin-resistant Staphylococcus aureus USA300. Int J Antimicrob Agents 39:402–406PubMedCrossRefGoogle Scholar
  22. 22.
    Wang G, Li X, Wang Z (2009) APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res 37:D933–D937PubMedCrossRefGoogle Scholar
  23. 23.
    Abbanat D, Morrow B, Bush K (2008) New agents in development for the treatment of bacterial infections. Curr Opin Pharmacol 8:582–592PubMedCrossRefGoogle Scholar
  24. 24.
    Hancock RE (1997) Peptide antibiotics. Lancet 349:418–422PubMedCrossRefGoogle Scholar
  25. 25.
    Diamond G, Beckloff N, Weinberg A, Kisich KO (2009) The roles of antimicrobial peptides in innate host defense. Curr Pharm Des 15:2377–2392PubMedCrossRefGoogle Scholar
  26. 26.
    Hancock RE, Diamond G (2000) The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol 8:402–410PubMedCrossRefGoogle Scholar
  27. 27.
    Barak O, Treat JR, James WD (2005) Antimicrobial peptides: effectors of innate immunity in the skin. Adv Dermatol 21:357–374PubMedCrossRefGoogle Scholar
  28. 28.
    Izadpanah A, Gallo RL (2005) Antimicrobial peptides. J Am Acad Dermatol 52:381–390, quiz 391–382PubMedCrossRefGoogle Scholar
  29. 29.
    Yin M, Gentili C, Koyama E, Zasloff M, Pacifici M (2002) Antiangiogenic treatment delays chondrocyte maturation and bone formation during limb skeletogenesis. J Bone Miner Res 17:56–65PubMedCrossRefGoogle Scholar
  30. 30.
    Nissen-Meyer J, Nes IF (1997) Ribosomally synthesized antimicrobial peptides: their function, structure, biogenesis, and mechanism of action. Arch Microbiol 167:67–77CrossRefGoogle Scholar
  31. 31.
    Papagianni M (2003) Ribosomally synthesized peptides with antimicrobial properties: biosynthesis, structure, function, and applications. Biotechnol Adv 21:465–499PubMedCrossRefGoogle Scholar
  32. 32.
    Berkowitz BA, Bevins CL, Zasloff MA (1990) Magainins: a new family of membrane-active host defense peptides. Biochem Pharmacol 39:625–629PubMedCrossRefGoogle Scholar
  33. 33.
    Boggs JM, Jo E, Polozov IV, Epand RF, Anantharamaiah GM, Blazyk J, Epand RM (2001) Effect of magainin, class L, and class A amphipathic peptides on fatty acid spin labels in lipid bilayers. Biochim Biophys Acta 1511:28–41PubMedCrossRefGoogle Scholar
  34. 34.
    Porcelli F, Buck-Koehntop BA, Thennarasu S, Ramamoorthy A, Veglia G (2006) Structures of the dimeric and monomeric variants of magainin antimicrobial peptides (MSI-78 and MSI-594) in micelles and bilayers, determined by NMR spectroscopy. Biochemistry 45:5793–5799PubMedCrossRefGoogle Scholar
  35. 35.
    Ramamoorthy A, Thennarasu S, Lee DK, Tan A, Maloy L (2006) Solid-state NMR investigation of the membrane-disrupting mechanism of antimicrobial peptides MSI-78 and MSI-594 derived from magainin 2 and melittin. Biophys J 91:206–216PubMedCrossRefGoogle Scholar
  36. 36.
    Zasloff M (1987) Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc Natl Acad Sci USA 84:5449–5453PubMedCrossRefGoogle Scholar
  37. 37.
    Nijnik A, Hancock RE (2009) The roles of cathelicidin LL-37 in immune defences and novel clinical applications. Curr Opin Hematol 16:41–47PubMedCrossRefGoogle Scholar
  38. 38.
    Porcelli F, Verardi R, Shi L, Henzler-Wildman KA, Ramamoorthy A, Veglia G (2008) NMR structure of the cathelicidin-derived human antimicrobial peptide LL-37 in dodecylphosphocholine micelles. Biochemistry 47:5565–5572PubMedCrossRefGoogle Scholar
  39. 39.
    Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, Wilson JM (1998) Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 102:874–880PubMedCrossRefGoogle Scholar
  40. 40.
    Howell MD (2007) The role of human beta defensins and cathelicidins in atopic dermatitis. Curr Opin Allergy Clin Immunol 7:413–417PubMedCrossRefGoogle Scholar
  41. 41.
    Tang M, Waring AJ, Lehrer RI, Hong M (2006) Orientation of a beta-hairpin antimicrobial peptide in lipid bilayers from two-dimensional dipolar chemical-shift correlation NMR. Biophys J 90:3616–3624PubMedCrossRefGoogle Scholar
  42. 42.
    Steinstraesser L, Kraneburg UM, Hirsch T, Kesting M, Steinau HU, Jacobsen F, Al-Benna S (2009) Host defense peptides as effector molecules of the innate immune response: a sledgehammer for drug resistance? Int J Mol Sci 10:3951–3970PubMedCrossRefGoogle Scholar
  43. 43.
    Boman HG (1995) Peptide antibiotics and their role in innate immunity. Annu Rev Immunol 13:61–92PubMedCrossRefGoogle Scholar
  44. 44.
    Guani-Guerra E, Santos-Mendoza T, Lugo-Reyes SO, Teran LM (2010) Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin Immunol 135:1–11PubMedCrossRefGoogle Scholar
  45. 45.
    Buffy JJ, Hong T, Yamaguchi S, Waring AJ, Lehrer RI, Hong M (2003) Solid-state NMR investigation of the depth of insertion of protegrin-1 in lipid bilayers using paramagnetic Mn2+. Biophys J 85:2363–2373PubMedCrossRefGoogle Scholar
  46. 46.
    Chekmenev EY, Jones SM, Nikolayeva YN, Vollmar BS, Wagner TJ, Gor’kov PL, Brey WW, Manion MN, Daugherty KC, Cotten M (2006) High-field NMR studies of molecular recognition and structure-function relationships in antimicrobial piscidins at the water-lipid bilayer interface. J Am Chem Soc 128:5308–5309PubMedCrossRefGoogle Scholar
  47. 47.
    Bonev BB, Chan WC, Bycroft BW, Roberts GC, Watts A (2000) Interaction of the lantibiotic nisin with mixed lipid bilayers: a 31P and 2H NMR study. Biochemistry 39:11425–11433PubMedCrossRefGoogle Scholar
  48. 48.
    Almeida PF, Pokorny A (2009) Mechanisms of antimicrobial, cytolytic, and cell-penetrating peptides: from kinetics to thermodynamics. Biochemistry 48:8083–8093PubMedCrossRefGoogle Scholar
  49. 49.
    Bechinger B (2011) Insights into the mechanisms of action of host defence peptides from biophysical and structural investigations. J Pept Sci 17:306–314PubMedCrossRefGoogle Scholar
  50. 50.
    Brogden KA (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3:238–250PubMedCrossRefGoogle Scholar
  51. 51.
    Dathe M, Wieprecht T (1999) Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells. Biochim Biophys Acta 1462:71–87PubMedCrossRefGoogle Scholar
  52. 52.
    Bechinger B, Salnikov ES (2012) The membrane interactions of antimicrobial peptides revealed by solid-state NMR spectroscopy. Chem Phys Lipids 165:282–301PubMedCrossRefGoogle Scholar
  53. 53.
    Blazyk J, Wiegand R, Klein J, Hammer J, Epand RM, Epand RF, Maloy WL, Kari UP (2001) A novel linear amphipathic beta-sheet cationic antimicrobial peptide with enhanced selectivity for bacterial lipids. J Biol Chem 276:27899–27906PubMedCrossRefGoogle Scholar
  54. 54.
    Epand RF, Epand RM, Monaco V, Stoia S, Formaggio F, Crisma M, Toniolo C (1999) The antimicrobial peptide trichogin and its interaction with phospholipid membranes. Eur J Biochem 266:1021–1028PubMedCrossRefGoogle Scholar
  55. 55.
    Boland MP, Separovic F (2006) Membrane interactions of antimicrobial peptides from Australian tree frogs. Biochim Biophys Acta 1758:1178–1183PubMedCrossRefGoogle Scholar
  56. 56.
    Epand RF, Umezawa N, Porter EA, Gellman SH, Epand RM (2003) Interactions of the antimicrobial beta-peptide beta-17 with phospholipid vesicles differ from membrane interactions of magainins. Eur J Biochem 270:1240–1248PubMedCrossRefGoogle Scholar
  57. 57.
    Fernandez DI, Sani MA, Gehman JD, Hahm KS, Separovic F (2011) Interactions of a synthetic Leu-Lys-rich antimicrobial peptide with phospholipid bilayers. Eur Biophys J 40:471–480PubMedCrossRefGoogle Scholar
  58. 58.
    Gazit E, Boman A, Boman HG, Shai Y (1995) Interaction of the mammalian antibacterial peptide cecropin P1 with phospholipid vesicles. Biochemistry 34:11479–11488PubMedCrossRefGoogle Scholar
  59. 59.
    Jiang Z, Kullberg BJ, van der Lee H, Vasil AI, Hale JD, Mant CT, Hancock RE, Vasil ML, Netea MG, Hodges RS (2008) Effects of hydrophobicity on the antifungal activity of alpha-helical antimicrobial peptides. Chem Biol Drug Des 72:483–495PubMedCrossRefGoogle Scholar
  60. 60.
    Dathe M, Wieprecht T, Nikolenko H, Handel L, Maloy WL, MacDonald DL, Beyermann M, Bienert M (1997) Hydrophobicity, hydrophobic moment and angle subtended by charged residues modulate antibacterial and haemolytic activity of amphipathic helical peptides. FEBS Lett 403:208–212PubMedCrossRefGoogle Scholar
  61. 61.
    Hancock RE, Rozek A (2002) Role of membranes in the activities of antimicrobial cationic peptides. FEMS Microbiol Lett 206:143–149PubMedCrossRefGoogle Scholar
  62. 62.
    Almeida PF, Pokorny A (2010) Binding and permeabilization of model membranes by amphipathic peptides. Methods Mol Biol 618:155–169PubMedCrossRefGoogle Scholar
  63. 63.
    Epand RF, Pollard JE, Wright JO, Savage PB, Epand RM (2010) Depolarization, bacterial membrane composition, and the antimicrobial action of ceragenins. Antimicrob Agents Chemother 54:3708–3713PubMedCrossRefGoogle Scholar
  64. 64.
    Epand RF, Schmitt MA, Gellman SH, Epand RM (2006) Role of membrane lipids in the mechanism of bacterial species selective toxicity by two alpha/beta-antimicrobial peptides. Biochim Biophys Acta 1758:1343–1350PubMedCrossRefGoogle Scholar
  65. 65.
    Shai Y (2002) Mode of action of membrane active antimicrobial peptides. Biopolymers 66:236–248PubMedCrossRefGoogle Scholar
  66. 66.
    Shai Y (1999) Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta 1462:55–70PubMedCrossRefGoogle Scholar
  67. 67.
    Papo N, Shai Y (2003) Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes? Peptides 24:1693–1703PubMedCrossRefGoogle Scholar
  68. 68.
    Teixeira V, Feio MJ, Bastos M (2012) Role of lipids in the interaction of antimicrobial peptides with membranes. Prog Lipid Res 51:149–177PubMedCrossRefGoogle Scholar
  69. 69.
    Epand RM, Epand RF (2011) Bacterial membrane lipids in the action of antimicrobial agents. J Pept Sci 17:298–305PubMedCrossRefGoogle Scholar
  70. 70.
    Aisenbrey C, Bertani P, Bechinger B (2010) Solid-state NMR investigations of membrane-associated antimicrobial peptides. Methods Mol Biol 618:209–233PubMedCrossRefGoogle Scholar
  71. 71.
    Bechinger B (2010) Membrane association and pore formation by alpha-helical peptides. Adv Exp Med Biol 677:24–30PubMedCrossRefGoogle Scholar
  72. 72.
    Huang HW (2006) Molecular mechanism of antimicrobial peptides: the origin of cooperativity. Biochim Biophys Acta 1758:1292–1302PubMedCrossRefGoogle Scholar
  73. 73.
    Huang HW (2000) Action of antimicrobial peptides: two-state model. Biochemistry 39:8347–8352PubMedCrossRefGoogle Scholar
  74. 74.
    Bechinger B (2000) Biophysical investigations of membrane perturbations by polypeptides using solid-state NMR spectroscopy (review). Mol Membr Biol 17:135–142PubMedCrossRefGoogle Scholar
  75. 75.
    Chen FY, Lee MT, Huang HW (2003) Evidence for membrane thinning effect as the mechanism for peptide-induced pore formation. Biophys J 84:3751–3758PubMedCrossRefGoogle Scholar
  76. 76.
    Pabst G, Grage SL, Danner-Pongratz S, Jing W, Ulrich AS, Watts A, Lohner K, Hickel A (2008) Membrane thickening by the antimicrobial peptide PGLa. Biophys J 95:5779–5788PubMedCrossRefGoogle Scholar
  77. 77.
    Nomura K, Corzo G (2006) The effect of binding of spider-derived antimicrobial peptides, oxyopinins, on lipid membranes. Biochim Biophys Acta 1758:1475–1482PubMedCrossRefGoogle Scholar
  78. 78.
    Nomura K, Corzo G, Nakajima T, Iwashita T (2004) Orientation and pore-forming mechanism of a scorpion pore-forming peptide bound to magnetically oriented lipid bilayers. Biophys J 87:2497–2507PubMedCrossRefGoogle Scholar
  79. 79.
    Smith PE, Brender JR, Ramamoorthy A (2009) Induction of negative curvature as a mechanism of cell toxicity by amyloidogenic peptides: the case of islet amyloid polypeptide. J Am Chem Soc 131:4470–4478PubMedCrossRefGoogle Scholar
  80. 80.
    Wieprecht T, Beyermann M, Seelig J (2002) Thermodynamics of the coil-alpha-helix transition of amphipathic peptides in a membrane environment: the role of vesicle curvature. Biophys Chem 96:191–201PubMedCrossRefGoogle Scholar
  81. 81.
    Wi S, Kim C (2008) Pore structure, thinning effect, and lateral diffusive dynamics of oriented lipid membranes interacting with antimicrobial peptide protegrin-1: 31P and 2H solid-state NMR study. J Phys Chem B 112:11402–11414PubMedCrossRefGoogle Scholar
  82. 82.
    White SH, Wimley WC (1999) Membrane protein folding and stability: physical principles. Annu Rev Biophys Biomol Struct 28:319–365PubMedCrossRefGoogle Scholar
  83. 83.
    Seelig J (2004) Thermodynamics of lipid-peptide interactions. Biochim Biophys Acta 1666:40–50PubMedCrossRefGoogle Scholar
  84. 84.
    Wimley WC (2010) Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem Biol 5:905–917PubMedCrossRefGoogle Scholar
  85. 85.
    Hristova K, Wimley WC (2011) A look at arginine in membranes. J Membr Biol 239:49–56PubMedCrossRefGoogle Scholar
  86. 86.
    Oren Z, Shai Y (1998) Mode of action of linear amphipathic alpha-helical antimicrobial peptides. Biopolymers 47:451–463PubMedCrossRefGoogle Scholar
  87. 87.
    Shai Y, Oren Z (2001) From “carpet” mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides. Peptides 22:1629–1641PubMedCrossRefGoogle Scholar
  88. 88.
    Avrahami D, Oren Z, Shai Y (2001) Effect of multiple aliphatic amino acids substitutions on the structure, function, and mode of action of diastereomeric membrane active peptides. Biochemistry 40:12591–12603PubMedCrossRefGoogle Scholar
  89. 89.
    Pokorny A, Almeida PF (2004) Kinetics of dye efflux and lipid flip-flop induced by delta-lysin in phosphatidylcholine vesicles and the mechanism of graded release by amphipathic, alpha-helical peptides. Biochemistry 43:8846–8857PubMedCrossRefGoogle Scholar
  90. 90.
    Oren Z, Lerman JC, Gudmundsson GH, Agerberth B, Shai Y (1999) Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem J 341(Pt 3):501–513PubMedCrossRefGoogle Scholar
  91. 91.
    He K, Ludtke SJ, Worcester DL, Huang HW (1996) Neutron scattering in the plane of membranes: structure of alamethicin pores. Biophys J 70:2659–2666PubMedCrossRefGoogle Scholar
  92. 92.
    Gehman JD, Luc F, Hall K, Lee TH, Boland MP, Pukala TL, Bowie JH, Aguilar MI, Separovic F (2008) Effect of antimicrobial peptides from Australian tree frogs on anionic phospholipid membranes. Biochemistry 47:8557–8565PubMedCrossRefGoogle Scholar
  93. 93.
    Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35:13723–13728PubMedCrossRefGoogle Scholar
  94. 94.
    Yang L, Harroun TA, Weiss TM, Ding L, Huang HW (2001) Barrel-stave model or toroidal model? A case study on melittin pores. Biophys J 81:1475–1485PubMedCrossRefGoogle Scholar
  95. 95.
    Epand RF, Maloy L, Ramamoorthy A, Epand RM (2010) Amphipathic helical cationic antimicrobial peptides promote rapid formation of crystalline states in the presence of phosphatidylglycerol: lipid clustering in anionic membranes. Biophys J 98:2564–2573PubMedCrossRefGoogle Scholar
  96. 96.
    Epand RF, Maloy WL, Ramamoorthy A, Epand RM (2010) Probing the “charge cluster mechanism” in amphipathic helical cationic antimicrobial peptides. Biochemistry 49:4076–4084PubMedCrossRefGoogle Scholar
  97. 97.
    Pag U, Oedenkoven M, Sass V, Shai Y, Shamova O, Antcheva N, Tossi A, Sahl HG (2008) Analysis of in vitro activities and modes of action of synthetic antimicrobial peptides derived from an alpha-helical ‘sequence template’. J Antimicrob Chemother 61:341–352PubMedCrossRefGoogle Scholar
  98. 98.
    Wieprecht T, Apostolov O, Beyermann M, Seelig J (2000) Membrane binding and pore formation of the antibacterial peptide PGLa: thermodynamic and mechanistic aspects. Biochemistry 39:442–452PubMedCrossRefGoogle Scholar
  99. 99.
    Yandek LE, Pokorny A, Floren A, Knoelke K, Langel U, Almeida PF (2007) Mechanism of the cell-penetrating peptide transportan 10 permeation of lipid bilayers. Biophys J 92:2434–2444PubMedCrossRefGoogle Scholar
  100. 100.
    Ladokhin AS, Wimley WC, Hristova K, White SH (1997) Mechanism of leakage of contents of membrane vesicles determined by fluorescence requenching. Methods Enzymol 278:474–486PubMedCrossRefGoogle Scholar
  101. 101.
    Ladokhin AS, Wimley WC, White SH (1995) Leakage of membrane vesicle contents: determination of mechanism using fluorescence requenching. Biophys J 69:1964–1971PubMedCrossRefGoogle Scholar
  102. 102.
    Gregory SM, Cavenaugh A, Journigan V, Pokorny A, Almeida PF (2008) A quantitative model for the all-or-none permeabilization of phospholipid vesicles by the antimicrobial peptide cecropin A. Biophys J 94:1667–1680PubMedCrossRefGoogle Scholar
  103. 103.
    Gregory SM, Pokorny A, Almeida PF (2009) Magainin 2 revisited: a test of the quantitative model for the all-or-none permeabilization of phospholipid vesicles. Biophys J 96:116–131PubMedCrossRefGoogle Scholar
  104. 104.
    Wimley WC, Selsted ME, White SH (1994) Interactions between human defensins and lipid bilayers: evidence for formation of multimeric pores. Protein Sci 3:1362–1373PubMedCrossRefGoogle Scholar
  105. 105.
    Epand RM, Vogel HJ (1999) Diversity of antimicrobial peptides and their mechanisms of action. Biochim Biophys Acta 1462:11–28PubMedCrossRefGoogle Scholar
  106. 106.
    Koprivnjak T, Peschel A (2011) Bacterial resistance mechanisms against host defense peptides. Cell Mol Life Sci 68:2243–2254PubMedCrossRefGoogle Scholar
  107. 107.
    Marion D, Zasloff M, Bax A (1988) A two-dimensional NMR study of the antimicrobial peptide magainin 2. FEBS Lett 227:21–26PubMedCrossRefGoogle Scholar
  108. 108.
    Bechinger B (1999) The structure, dynamics and orientation of antimicrobial peptides in membranes by multidimensional solid-state NMR spectroscopy. Biochim Biophys Acta 1462:157–183PubMedCrossRefGoogle Scholar
  109. 109.
    Hauge HH, Mantzilas D, Eijsink VG, Nissen-Meyer J (1999) Membrane-mimicking entities induce structuring of the two-peptide bacteriocins plantaricin E/F and plantaricin J/K. J Bacteriol 181:740–747PubMedGoogle Scholar
  110. 110.
    Luo P, Baldwin RL (1997) Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol/water mixtures back to water. Biochemistry 36:8413–8421PubMedCrossRefGoogle Scholar
  111. 111.
    Prosser RS, Evanics F, Kitevski JL, Al-Abdul-Wahid MS (2006) Current applications of bicelles in NMR studies of membrane-associated amphiphiles and proteins. Biochemistry 45:8453–8465PubMedCrossRefGoogle Scholar
  112. 112.
    Warschawski DE, Arnold AA, Beaugrand M, Gravel A, Chartrand E, Marcotte I (2011) Choosing membrane mimetics for NMR structural studies of transmembrane proteins. Biochim Biophys Acta 1808:1957–1974PubMedCrossRefGoogle Scholar
  113. 113.
    Bourbigot S, Fardy L, Waring AJ, Yeaman MR, Booth V (2009) Structure of chemokine-derived antimicrobial peptide interleukin-8alpha and interaction with detergent micelles and oriented lipid bilayers. Biochemistry 48:10509–10521PubMedCrossRefGoogle Scholar
  114. 114.
    Khandelia H, Kaznessis YN (2005) Molecular dynamics simulations of helical antimicrobial peptides in SDS micelles: what do point mutations achieve? Peptides 26:2037–2049PubMedCrossRefGoogle Scholar
  115. 115.
    Mascioni A, Porcelli F, Ilangovan U, Ramamoorthy A, Veglia G (2003) Conformational preferences of the amylin nucleation site in SDS micelles: an NMR study. Biopolymers 69:29–41PubMedCrossRefGoogle Scholar
  116. 116.
    Buffy JJ, Buck-Koehntop BA, Porcelli F, Traaseth NJ, Thomas DD, Veglia G (2006) Defining the intramembrane binding mechanism of sarcolipin to calcium ATPase using solution NMR spectroscopy. J Mol Biol 358:420–429PubMedCrossRefGoogle Scholar
  117. 117.
    Sherman PJ, Jackway RJ, Gehman JD, Praporski S, McCubbin GA, Mechler A, Martin LL, Separovic F, Bowie JH (2009) Solution structure and membrane interactions of the antimicrobial peptide fallaxidin 4.1a: an NMR and QCM study. Biochemistry 48:11892–11901PubMedCrossRefGoogle Scholar
  118. 118.
    Poget SF, Cahill SM, Girvin ME (2007) Isotropic bicelles stabilize the functional form of a small multidrug-resistance pump for NMR structural studies. J Am Chem Soc 129:2432–2433PubMedCrossRefGoogle Scholar
  119. 119.
    Sanders CR 2nd, Landis GC (1995) Reconstitution of membrane proteins into lipid-rich bilayered mixed micelles for NMR studies. Biochemistry 34:4030–4040PubMedCrossRefGoogle Scholar
  120. 120.
    Sanders CR, Prosser RS (1998) Bicelles: a model membrane system for all seasons? Structure 6:1227–1234PubMedCrossRefGoogle Scholar
  121. 121.
    Marcotte I, Wegener KL, Lam YH, Chia BC, de Planque MR, Bowie JH, Auger M, Separovic F (2003) Interaction of antimicrobial peptides from Australian amphibians with lipid membranes. Chem Phys Lipids 122: 107–120PubMedCrossRefGoogle Scholar
  122. 122.
    Dittmer J, Thogersen L, Underhaug J, Bertelsen K, Vosegaard T, Pedersen JM, Schiott B, Tajkhorshid E, Skrydstrup T, Nielsen NC (2009) Incorporation of antimicrobial peptides into membranes: a combined liquid-state NMR and molecular dynamics study of alamethicin in DMPC/DHPC bicelles. J Phys Chem B 113:6928–6937PubMedCrossRefGoogle Scholar
  123. 123.
    Jiang Y, Wang H, Kindt JT (2010) Atomistic simulations of bicelle mixtures. Biophys J 98:2895–2903PubMedCrossRefGoogle Scholar
  124. 124.
    van Dam L, Karlsson G, Edwards K (2006) Morphology of magnetically aligning DMPC/DHPC aggregates-perforated sheets, not disks. Langmuir 22:3280–3285PubMedCrossRefGoogle Scholar
  125. 125.
    Bechinger B (2005) Detergent-like properties of magainin antibiotic peptides: a 31P solid-state NMR spectroscopy study. Biochim Biophys Acta 1712:101–108PubMedCrossRefGoogle Scholar
  126. 126.
    Cardon TB, Tiburu EK, Lorigan GA (2003) Magnetically aligned phospholipid bilayers in weak magnetic fields: optimization, mechanism, and advantages for X-band EPR studies. J Magn Reson 161:77–90PubMedCrossRefGoogle Scholar
  127. 127.
    Diller A, Loudet C, Aussenac F, Raffard G, Fournier S, Laguerre M, Grelard A, Opella SJ, Marassi FM, Dufourc EJ (2009) Bicelles: a natural ‘molecular goniometer’ for structural, dynamical and topological studies of molecules in membranes. Biochimie 91:744–751PubMedCrossRefGoogle Scholar
  128. 128.
    De Angelis AA, Grant CV, Baxter MK, McGavin JA, Opella SJ, Cotten ML (2011) Amphipathic antimicrobial piscidin in magnetically aligned lipid bilayers. Biophys J 101:1086–1094PubMedCrossRefGoogle Scholar
  129. 129.
    Verardi R, Traaseth NJ, Shi L, Porcelli F, Monfregola L, De Luca S, Amodeo P, Veglia G, Scaloni A (2012) Probing membrane topology of the antimicrobial peptide distinctin by solid-state NMR spectroscopy in zwitterionic and charged lipid bilayers. Biochim Biophys Acta 1808:34–40Google Scholar
  130. 130.
    Mote KR, Gopinath T, Traaseth NJ, Kitchen J, Gor’kov PL, Brey WW, Veglia G (2011) Multidimensional oriented solid-state NMR experiments enable the sequential assignment of uniformly 15N labeled integral membrane proteins in magnetically aligned lipid bilayers. J Biomol NMR 51:339–346PubMedCrossRefGoogle Scholar
  131. 131.
    Bechinger B, Kim Y, Chirlian LE, Gesell J, Neumann JM, Montal M, Tomich J, Zasloff M, Opella SJ (1991) Orientations of amphipathic helical peptides in membrane bilayers determined by solid-state NMR spectroscopy. J Biomol NMR 1:167–173PubMedCrossRefGoogle Scholar
  132. 132.
    Opella SJ, Ma C, Marassi FM (2001) Nuclear magnetic resonance of membrane-associated peptides and proteins. Methods Enzymol 339:285–313PubMedCrossRefGoogle Scholar
  133. 133.
    Valentine KG, Liu SF, Marassi FM, Veglia G, Opella SJ, Ding FX, Wang SH, Arshava B, Becker JM, Naider F (2001) Structure and topology of a peptide segment of the 6th transmembrane domain of the Saccharomyces cerevisae alpha-factor receptor in phospholipid bilayers. Biopolymers 59:243–256PubMedCrossRefGoogle Scholar
  134. 134.
    Killian JA, Borle F, de Kruijff B, Seelig J (1986) Comparative 2H- and 31P-NMR study on the properties of palmitoyllysophosphatidylcholine in bilayers with gramicidin, cholesterol and dipalmitoylphosphatidylcholine. Biochim Biophys Acta 854:133–142PubMedCrossRefGoogle Scholar
  135. 135.
    Klocek G, Schulthess T, Shai Y, Seelig J (2009) Thermodynamics of melittin binding to lipid bilayers. Aggregation and pore formation. Biochemistry 48:2586–2596PubMedCrossRefGoogle Scholar
  136. 136.
    Seelig J, MacDonald PM (1987) Phospholipids and proteins in biological membranes. 2H NMR as a method to study structure, dynamics, and interactions. Acc Chem Res 20:221–228CrossRefGoogle Scholar
  137. 137.
    Sharma M, Yi M, Dong H, Qin H, Peterson E, Busath DD, Zhou HX, Cross TA (2010) Insight into the mechanism of the influenza A proton channel from a structure in a lipid bilayer. Science 330:509–512PubMedCrossRefGoogle Scholar
  138. 138.
    Mascioni A, Karim C, Barany G, Thomas DD, Veglia G (2002) Structure and orientation of sarcolipin in lipid environments. Biochemistry 41:475–482PubMedCrossRefGoogle Scholar
  139. 139.
    Mascioni A, Karim C, Zamoon J, Thomas DD, Veglia G (2002) Solid-state NMR and rigid body molecular dynamics to determine domain orientations of monomeric phospholamban. J Am Chem Soc 124:9392–9393PubMedCrossRefGoogle Scholar
  140. 140.
    Traaseth NJ, Buffy JJ, Zamoon J, Veglia G (2006) Structural dynamics and topology of phospholamban in oriented lipid bilayers using multidimensional solid-state NMR. Biochemistry 45:13827–13834PubMedCrossRefGoogle Scholar
  141. 141.
    Traaseth NJ, Shi L, Verardi R, Mullen DG, Barany G, Veglia G (2009) Structure and topology of monomeric phospholamban in lipid membranes determined by a hybrid solution and solid-state NMR approach. Proc Natl Acad Sci USA 106:10165–10170PubMedCrossRefGoogle Scholar
  142. 142.
    Verardi R, Shi L, Traaseth NJ, Walsh N, Veglia G (2011) Structural topology of phospholamban pentamer in lipid bilayers by a hybrid solution and solid-state NMR method. Proc Natl Acad Sci USA 108:9101–9106PubMedCrossRefGoogle Scholar
  143. 143.
    Epand RM, Epand RF (2003) Liposomes as models for antimicrobial peptides. Methods Enzymol 372:124–133PubMedCrossRefGoogle Scholar
  144. 144.
    Marquette A, Lorber B, Bechinger B (2010) Reversible liposome association induced by LAH4: a peptide with potent antimicrobial and nucleic acid transfection activities. Biophys J 98:2544–2553PubMedCrossRefGoogle Scholar
  145. 145.
    Georgescu J, Munhoz VH, Bechinger B (2010) NMR structures of the histidine-rich peptide LAH4 in micellar environments: membrane insertion, pH-dependent mode of antimicrobial action, and DNA transfection. Biophys J 99:2507–2515PubMedCrossRefGoogle Scholar
  146. 146.
    Malliavin TE, Giudice E (2002) Analysis of peptide rotational diffusion by homonuclear NMR. Biopolymers 63:335–342PubMedCrossRefGoogle Scholar
  147. 147.
    Porcelli F, Buck B, Lee DK, Hallock KJ, Ramamoorthy A, Veglia G (2004) Structure and orientation of pardaxin determined by NMR experiments in model membranes. J Biol Chem 279:45815–45823PubMedCrossRefGoogle Scholar
  148. 148.
    Park SH, Kim YK, Park JW, Lee B, Lee BJ (2000) Solution structure of the antimicrobial peptide gaegurin 4 by H and 15N nuclear magnetic resonance spectroscopy. Eur J Biochem 267:2695–2704PubMedCrossRefGoogle Scholar
  149. 149.
    Matsumori N, Murata M (2010) 3D structures of membrane-associated small molecules as determined in isotropic bicelles. Nat Prod Rep 27:1480–1492PubMedCrossRefGoogle Scholar
  150. 150.
    Yamamoto K, Vivekanandan S, Ramamoorthy A (2011) Fast NMR data acquisition from bicelles containing a membrane-associated peptide at natural-abundance. J Phys Chem B 115:12448–12455PubMedCrossRefGoogle Scholar
  151. 151.
    Chou JJ, Delaglio F, Bax A (2000) Measurement of one-bond 15N-13C′ dipolar couplings in medium sized proteins. J Biomol NMR 18:101–105PubMedCrossRefGoogle Scholar
  152. 152.
    Kubat JA, Chou JJ, Rovnyak D (2007) Nonuniform sampling and maximum entropy reconstruction applied to the accurate measurement of residual dipolar couplings. J Magn Reson 186:201–211PubMedCrossRefGoogle Scholar
  153. 153.
    Jaroniec CP, Boisbouvier J, Tworowska I, Nikonowicz EP, Bax A (2005) Accurate measurement of 15N-13C residual dipolar couplings in nucleic acids. J Biomol NMR 31:231–241PubMedCrossRefGoogle Scholar
  154. 154.
    Al-Abdul-Wahid MS, Verardi R, Veglia G, Prosser RS (2011) Topology and immersion depth of an integral membrane protein by paramagnetic rates from dissolved oxygen. J Biomol NMR 51:173–183PubMedCrossRefGoogle Scholar
  155. 155.
    Donghi D, Sigel RK (2012) Metal ion-RNA interactions studied via multinuclear NMR. Methods Mol Biol 848:253–273PubMedCrossRefGoogle Scholar
  156. 156.
    Glover KJ, Whiles JA, Vold RR, Melacini G (2002) Position of residues in transmembrane peptides with respect to the lipid bilayer: a combined lipid Noes and water chemical exchange approach in phospholipid bicelles. J Biomol NMR 22:57–64PubMedCrossRefGoogle Scholar
  157. 157.
    Huang H, Melacini G (2006) High-resolution protein hydration NMR experiments: probing how protein surfaces interact with water and other non-covalent ligands. Anal Chim Acta 564:1–9PubMedCrossRefGoogle Scholar
  158. 158.
    Melacini G, Boelens R, Kaptein R (1999) Band-selective editing of exchange-relay in protein-water NOE experiments. J Biomol NMR 13:67–71PubMedCrossRefGoogle Scholar
  159. 159.
    Choutko A, Glattli A, Fernandez C, Hilty C, Wuthrich K, van Gunsteren WF (2010) Membrane protein dynamics in different environments: simulation study of the outer membrane protein X in a lipid bilayer and in a micelle. Eur Biophys J 40:39–58PubMedCrossRefGoogle Scholar
  160. 160.
    Fernandez C, Adeishvili K, Wuthrich K (2001) Transverse relaxation-optimized NMR spectroscopy with the outer membrane protein OmpX in dihexanoyl phosphatidylcholine micelles. Proc Natl Acad Sci USA 98:2358–2363PubMedCrossRefGoogle Scholar
  161. 161.
    Fernandez C, Hilty C, Wider G, Wuthrich K (2002) Lipid-protein interactions in DHPC micelles containing the integral membrane protein OmpX investigated by NMR spectroscopy. Proc Natl Acad Sci USA 99:13533–13537PubMedCrossRefGoogle Scholar
  162. 162.
    Fernandez C, Wuthrich K (2003) NMR solution structure determination of membrane proteins reconstituted in detergent micelles. FEBS Lett 555:144–150PubMedCrossRefGoogle Scholar
  163. 163.
    Nishida N, Shimada I (2011) An NMR method to study protein-protein interactions. Methods Mol Biol 757:129–137CrossRefGoogle Scholar
  164. 164.
    Shimada I (2005) NMR techniques for identifying the interface of a larger protein-protein complex: cross-saturation and transferred cross-saturation experiments. Methods Enzymol 394:483–506PubMedCrossRefGoogle Scholar
  165. 165.
    Takahashi H, Miyazawa M, Ina Y, Fukunishi Y, Mizukoshi Y, Nakamura H, Shimada I (2006) Utilization of methyl proton resonances in cross-saturation measurement for determining the interfaces of large protein-protein complexes. J Biomol NMR 34:167–177PubMedCrossRefGoogle Scholar
  166. 166.
    Cook GA, Zhang H, Park SH, Wang Y, Opella SJ (2010) Comparative NMR studies demonstrate profound differences between two viroporins: p7 of HCV and Vpu of HIV-1. Biochim Biophys Acta 1808:554–560PubMedGoogle Scholar
  167. 167.
    Howard KP, Opella SJ (1996) High-resolution solid-state NMR spectra of integral membrane proteins reconstituted into magnetically oriented phospholipid bilayers. J Magn Reson B 112:91–94PubMedCrossRefGoogle Scholar
  168. 168.
    Gopinath T, Traaseth NJ, Mote K, Veglia G (2010) Sensitivity enhanced heteronuclear correlation spectroscopy in multidimensional solid-state NMR of oriented systems via chemical shift coherences. J Am Chem Soc 132:5357–5363PubMedCrossRefGoogle Scholar
  169. 169.
    Gopinath T, Veglia G (2012) Dual acquisition magic-angle spinning solid-state NMR-spectroscopy: simultaneous acquisition of multidimensional spectra of biomacromolecules. Angew Chem Int Ed Engl 51:2731–2735PubMedCrossRefGoogle Scholar
  170. 170.
    Bechinger B, Gierasch LM, Montal M, Zasloff M, Opella SJ (1996) Orientations of helical peptides in membrane bilayers by solid state NMR spectroscopy. Solid State Nucl Magn Reson 7:185–191PubMedCrossRefGoogle Scholar
  171. 171.
    Bechinger B, Skladnev DA, Ogrel A, Li X, Rogozhkina EV, Ovchinnikova TV, O’Neil JD, Raap J (2001) 15N and 31P solid-state NMR investigations on the orientation of zervamicin II and alamethicin in phosphatidylcholine membranes. Biochemistry 40:9428–9437PubMedCrossRefGoogle Scholar
  172. 172.
    Bechinger B, Zasloff M, Opella SJ (1993) Structure and orientation of the antibiotic peptide magainin in membranes by solid-state nuclear magnetic resonance spectroscopy. Protein Sci 2:2077–2084PubMedCrossRefGoogle Scholar
  173. 173.
    Gustavsson M, Traaseth NJ, Veglia G (2012) Probing ground and excited states of phospholamban in model and native lipid membranes by magic angle spinning NMR spectroscopy. Biochim Biophys Acta 1818:146–153PubMedCrossRefGoogle Scholar
  174. 174.
    Tang M, Hong M (2009) Structure and mechanism of beta-hairpin antimicrobial peptides in lipid bilayers from solid-state NMR spectroscopy. Mol Biosyst 5:317–322PubMedCrossRefGoogle Scholar
  175. 175.
    Yamaguchi S, Huster D, Waring A, Lehrer RI, Kearney W, Tack BF, Hong M (2001) Orientation and dynamics of an antimicrobial peptide in the lipid bilayer by solid-state NMR spectroscopy. Biophys J 81:2203–2214PubMedCrossRefGoogle Scholar
  176. 176.
    Ramamoorthy A, Lee DK, Santos JS, Henzler-Wildman KA (2008) Nitrogen-14 solid-state NMR spectroscopy of aligned phospholipid bilayers to probe peptide-lipid interaction and oligomerization of membrane associated peptides. J Am Chem Soc 130:11023–11029PubMedCrossRefGoogle Scholar
  177. 177.
    Thennarasu S, Lee DK, Poon A, Kawulka KE, Vederas JC, Ramamoorthy A (2005) Membrane permeabilization, orientation, and antimicrobial mechanism of subtilosin A. Chem Phys Lipids 137:38–51PubMedCrossRefGoogle Scholar
  178. 178.
    Ketchem RR, Hu W, Cross TA (1993) High-resolution conformation of gramicidin A in a lipid bilayer by solid-state NMR. Science 261:1457–1460PubMedCrossRefGoogle Scholar
  179. 179.
    Quine JR, Brenneman MT, Cross TA (1997) Protein structural analysis from solid-state NMR-derived orientational constraints. Biophys J 72:2342–2348PubMedCrossRefGoogle Scholar
  180. 180.
    Bechinger B, Kinder R, Helmle M, Vogt TC, Harzer U, Schinzel S (1999) Peptide structural analysis by solid-state NMR spectroscopy. Biopolymers 51:174–190PubMedCrossRefGoogle Scholar
  181. 181.
    Marassi FM, Ma C, Gesell JJ, Opella SJ (2000) Three-dimensional solid-state NMR spectroscopy is essential for resolution of resonances from in-plane residues in uniformly (15)N-labeled helical membrane proteins in oriented lipid bilayers. J Magn Reson 144:156–161PubMedCrossRefGoogle Scholar
  182. 182.
    De Angelis AA, Nevzorov AA, Park SH, Howell SC, Mrse AA, Opella SJ (2004) High-resolution NMR spectroscopy of membrane proteins in aligned bicelles. J Am Chem Soc 126:15340–15341PubMedCrossRefGoogle Scholar
  183. 183.
    Andronesi OC, Pfeifer JR, Al-Momani L, Ozdirekcan S, Rijkers DT, Angerstein B, Luca S, Koert U, Killian JA, Baldus M (2004) Probing membrane protein orientation and structure using fast magic-angle-spinning solid-state NMR. J Biomol NMR 30:253–265PubMedCrossRefGoogle Scholar
  184. 184.
    Elena B, Hediger S, Emsley L (2003) Correlation of fast and slow chemical shift spinning sideband patterns under fast magic-angle spinning. J Magn Reson 160:40–46PubMedCrossRefGoogle Scholar
  185. 185.
    Griffin RG (1998) Dipolar recoupling in MAS spectra of biological solids. Nat Struct Biol 5(Suppl):508–512PubMedCrossRefGoogle Scholar
  186. 186.
    Zasloff M, Martin B, Chen HC (1988) Antimicrobial activity of synthetic magainin peptides and several analogues. Proc Natl Acad Sci USA 85:910–913PubMedCrossRefGoogle Scholar
  187. 187.
    Bechinger B, Zasloff M, Opella SJ (1998) Structure and dynamics of the antibiotic peptide PGLa in membranes by solution and solid-state nuclear magnetic resonance spectroscopy. Biophys J 74:981–987PubMedCrossRefGoogle Scholar
  188. 188.
    Bechinger B, Zasloff M, Opella SJ (1992) Structure and interactions of magainin antibiotic peptides in lipid bilayers: a solid-state nuclear magnetic resonance investigation. Biophys J 62:12–14PubMedCrossRefGoogle Scholar
  189. 189.
    Gesell J, Zasloff M, Opella SJ (1997) Two-dimensional 1H NMR experiments show that the 23-residue magainin antibiotic peptide is an alpha-helix in dodecylphosphocholine micelles, sodium dodecylsulfate micelles, and trifluoroethanol/water solution. J Biomol NMR 9:127–135PubMedCrossRefGoogle Scholar
  190. 190.
    Matsuzaki K, Mitani Y, Akada KY, Murase O, Yoneyama S, Zasloff M, Miyajima K (1998) Mechanism of synergism between antimicrobial peptides magainin 2 and PGLa. Biochemistry 37:15144–15153PubMedCrossRefGoogle Scholar
  191. 191.
    Ramamoorthy A, Marassi FM, Zasloff M, Opella SJ (1995) Three-dimensional solid-state NMR spectroscopy of a peptide oriented in membrane bilayers. J Biomol NMR 6:329–334PubMedCrossRefGoogle Scholar
  192. 192.
    Wieprecht T, Apostolov O, Seelig J (2000) Binding of the antibacterial peptide magainin 2 amide to small and large unilamellar vesicles. Biophys Chem 85:187–198PubMedCrossRefGoogle Scholar
  193. 193.
    Islam K, Hawser SP (1998) MSI-78 magainin pharmaceuticals. IDrugs 1:605–609PubMedGoogle Scholar
  194. 194.
    Yang P, Ramamoorthy A, Chen Z (2011) Membrane orientation of MSI-78 measured by sum frequency generation vibrational spectroscopy. Langmuir 27:7760–7767PubMedCrossRefGoogle Scholar
  195. 195.
    Domadia PN, Bhunia A, Ramamoorthy A, Bhattacharjya S (2010) Structure, interactions, and antibacterial activities of MSI-594 derived mutant peptide MSI-594F5A in lipopolysaccharide micelles: role of the helical hairpin conformation in outer-membrane permea-bilization. J Am Chem Soc 132:18417–18428PubMedCrossRefGoogle Scholar
  196. 196.
    Wakamatsu K, Takeda A, Tachi T, Matsuzaki K (2002) Dimer structure of magainin 2 bound to phospholipid vesicles. Biopolymers 64:314–327PubMedCrossRefGoogle Scholar
  197. 197.
    Henzler-Wildman KA, Martinez GV, Brown MF, Ramamoorthy A (2004) Perturbation of the hydrophobic core of lipid bilayers by the human antimicrobial peptide LL-37. Biochemistry 43:8459–8469PubMedCrossRefGoogle Scholar
  198. 198.
    Lazarovici P, Primor N, Loew LM (1986) Purification and pore-forming activity of two hydrophobic polypeptides from the secretion of the Red Sea Moses sole (Pardachirus marmoratus). J Biol Chem 261:16704–16713PubMedGoogle Scholar
  199. 199.
    Oren Z, Shai Y (1996) A class of highly potent antibacterial peptides derived from pardaxin, a pore-forming peptide isolated from Moses sole fish Pardachirus marmoratus. Eur J Biochem 237:303–310PubMedCrossRefGoogle Scholar
  200. 200.
    Bhunia A, Domadia PN, Torres J, Hallock KJ, Ramamoorthy A, Bhattacharjya S (2010) NMR structure of pardaxin, a pore-forming antimicrobial peptide, in lipopolysaccharide micelles: mechanism of outer membrane permeabilization. J Biol Chem 285:3883–3895PubMedCrossRefGoogle Scholar
  201. 201.
    Epand RF, Ramamoorthy A, Epand RM (2006) Membrane lipid composition and the interaction of pardaxin: the role of cholesterol. Protein Pept Lett 13:1–5PubMedGoogle Scholar
  202. 202.
    Hallock KJ, Lee DK, Omnaas J, Mosberg HI, Ramamoorthy A (2002) Membrane composition determines pardaxin’s mechanism of lipid bilayer disruption. Biophys J 83:1004–1013PubMedCrossRefGoogle Scholar
  203. 203.
    Hsu JC, Lin LC, Tzen JT, Chen JY (2011) Pardaxin-induced apoptosis enhances antitumor activity in HeLa cells. Peptides 32:1110–1116PubMedCrossRefGoogle Scholar
  204. 204.
    Lelkes PI, Lazarovici P (1988) Pardaxin induces aggregation but not fusion of phosphatidylserine vesicles. FEBS Lett 230:131–136PubMedCrossRefGoogle Scholar
  205. 205.
    Vad BS, Bertelsen K, Johansen CH, Pedersen JM, Skrydstrup T, Nielsen NC, Otzen DE (2010) Pardaxin permeabilizes vesicles more efficiently by pore formation than by disruption. Biophys J 98:576–585PubMedCrossRefGoogle Scholar
  206. 206.
    Yang J, Parkanzky PD, Bodner ML, Duskin CA, Weliky DP (2002) Application of REDOR subtraction for filtered MAS observation of labeled backbone carbons of membrane-bound fusion peptides. J Magn Reson 159:101–110PubMedCrossRefGoogle Scholar
  207. 207.
    Lee DK, Ramamoorthy A (1999) Determination of the solid-state conformations of polyalanine using magic-angle spinning NMR spectroscopy. J Phys Chem B 103:271–275CrossRefGoogle Scholar
  208. 208.
    Batista CV, Scaloni A, Rigden DJ, Silva LR, Rodrigues Romero A, Dukor R, Sebben A, Talamo F, Bloch C (2001) A novel heterodimeric antimicrobial peptide from the tree-frog Phyllomedusa distincta. FEBS Lett 494:85–89PubMedCrossRefGoogle Scholar
  209. 209.
    Becucci L, Papini M, Mullen D, Scaloni A, Veglia G, Guidelli R (2011) Probing membrane permeabilization by the antimicrobial peptide distinctin in mercury-supported biomimetic membranes. Biochim Biophys Acta 1808:2745–2752PubMedCrossRefGoogle Scholar
  210. 210.
    Cirioni O, Ghiselli R, Orlando F, Silvestri C, De Luca S, Salzano AM, Mocchegiani F, Saba V, Scalise G, Scaloni A, Giacometti A (2008) Efficacy of the amphibian peptide distinctin in a neutropenic mouse model of staphylococcal sepsis. Crit Care Med 36:2629–2633PubMedCrossRefGoogle Scholar
  211. 211.
    Raimondo D, Andreotti G, Saint N, Amodeo P, Renzone G, Sanseverino M, Zocchi I, Molle G, Motta A, Scaloni A (2005) A folding-dependent mechanism of antimicrobial peptide resistance to degradation unveiled by solution structure of distinctin. Proc Natl Acad Sci USA 102:6309–6314PubMedCrossRefGoogle Scholar
  212. 212.
    Dalla Serra M, Cirioni O, Vitale RM, Renzone G, Coraiola M, Giacometti A, Potrich C, Baroni E, Guella G, Sanseverino M, De Luca S, Scalise G, Amodeo P, Scaloni A (2008) Structural features of distinctin affecting peptide biological and biochemical properties. Biochemistry 47:7888–7899PubMedCrossRefGoogle Scholar
  213. 213.
    Shi L, Traaseth NJ, Verardi R, Cembran A, Gao J, Veglia G (2009) A refinement protocol to determine structure, topology, and depth of insertion of membrane proteins using hybrid solution and solid-state NMR restraints. J Biomol NMR 44:195–205PubMedCrossRefGoogle Scholar
  214. 214.
    Bals R, Wang X, Zasloff M, Wilson JM (1998) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci USA 95:9541–9546PubMedCrossRefGoogle Scholar
  215. 215.
    Wong CC, Zhang L, Ren SX, Shen J, Chan RL, Cho CH (2011) Antibacterial peptides and gastrointestinal diseases. Curr Pharm Des 17:1583–1586PubMedCrossRefGoogle Scholar
  216. 216.
    Wu WK, Wong CC, Li ZJ, Zhang L, Ren SX, Cho CH (2010) Cathelicidins in inflammation and tissue repair: potential therapeutic applications for gastrointestinal disorders. Acta Pharmacol Sin 31:1118–1122PubMedCrossRefGoogle Scholar
  217. 217.
    Cederlund A, Gudmundsson GH, Agerberth B (2011) Antimicrobial peptides important in innate immunity. FEBS J 278:3942–3951PubMedCrossRefGoogle Scholar
  218. 218.
    Tecle T, Tripathi S, Hartshorn KL (2010) Review: defensins and cathelicidins in lung immunity. Innate Immun 16:151–159PubMedCrossRefGoogle Scholar
  219. 219.
    Yamasaki K, Gallo RL (2011) Rosacea as a disease of cathelicidins and skin innate immunity. J Investig Dermatol Symp Proc 15:12–15PubMedCrossRefGoogle Scholar
  220. 220.
    Amatngalim GD, Nijnik A, Hiemstra PS, Hancock RE (2011) Cathelicidin peptide LL-37 modulates TREM-1 expression and inflammatory responses to microbial compounds. Inflammation 34:412–425PubMedCrossRefGoogle Scholar
  221. 221.
    Brown KL, Poon GF, Birkenhead D, Pena OM, Falsafi R, Dahlgren C, Karlsson A, Bylund J, Hancock RE, Johnson P (2011) Host defense peptide LL-37 selectively reduces proinflammatory macrophage responses. J Immunol 186:5497–5505PubMedCrossRefGoogle Scholar
  222. 222.
    Ramamoorthy A, Lee DK, Narasimhaswamy T, Nanga RP (2010) Cholesterol reduces pardaxin’s dynamics-a barrel-stave mechanism of membrane disruption investigated by solid-state NMR. Biochim Biophys Acta 1798:223–227PubMedCrossRefGoogle Scholar
  223. 223.
    Ramamoorthy A (2009) Beyond NMR spectra of antimicrobial peptides: dynamical images at atomic resolution and functional insights. Solid State Nucl Magn Reson 35:201–207PubMedCrossRefGoogle Scholar
  224. 224.
    Hong J, Oren Z, Shai Y (1999) Structure and organization of hemolytic and nonhemolytic diastereomers of antimicrobial peptides in membranes. Biochemistry 38:16963–16973PubMedCrossRefGoogle Scholar
  225. 225.
    Durr UH, Sudheendra US, Ramamoorthy A (2006) LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 1758:1408–1425PubMedCrossRefGoogle Scholar
  226. 226.
    Henzler Wildman KA, Lee DK, Ramamoorthy A (2003) Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37. Biochemistry 42:6545–6558PubMedCrossRefGoogle Scholar
  227. 227.
    Dubosclard V, Blondot ML, Eleouet JF, Bontems F, Sizun C (2011) 1H, 13C, and 15N resonance assignment of the central domain of hRSV transcription antitermination factor M2-1. Biomol NMR Assign 5:237–239PubMedCrossRefGoogle Scholar
  228. 228.
    Aisenbrey C, Pendem N, Guichard G, Bechinger B (2012) Solid state NMR studies of oligourea foldamers: interaction of 15N-labelled amphiphilic helices with oriented lipid membranes. Org Biomol Chem 10:1440–1447PubMedCrossRefGoogle Scholar
  229. 229.
    Pius J, Morrow MR, Booth V (2012) (2)H solid-state nuclear magnetic resonance investigation of whole Escherichia coli interacting with antimicrobial peptide MSI-78. Biochemistry 51:118–125PubMedCrossRefGoogle Scholar
  230. 230.
    Bertelsen K, Vad B, Nielsen EH, Hansen SK, Skrydstrup T, Otzen DE, Vosegaard T, Nielsen NC (2012) Long-term-stable ether-lipid vs conventional ester-lipid bicelles in oriented solid-state NMR: altered structural information in studies of antimicrobial peptides. J Phys Chem B 115:1767–1774CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Fernando Porcelli
    • 1
    • 2
  • Ayyalusamy Ramamoorthy
    • 3
  • George Barany
    • 1
  • Gianluigi Veglia
    • 1
    • 2
  1. 1.Department of ChemistryUniversity of MinnesotaMinneapolisUSA
  2. 2.Department of Biochemistry, Molecular Biology, & BiophysicsUniversity of MinnesotaMinneapolisUSA
  3. 3.Department of ChemistryUniversity of MichiganAnn ArborUSA

Personalised recommendations