Skip to main content
Log in

Melittin: a Membrane-active Peptide with Diverse Functions

  • Review Article
  • Published:
Bioscience Reports

Abstract

Melittin is the principal toxic component in the venom of the European honey bee Apis mellifera and is a cationic, hemolytic peptide. It is a small linear peptide composed of 26 amino acid residues in which the amino-terminal region is predominantly hydrophobic whereas the carboxy-terminal region is hydrophilic due to the presence of a stretch of positively charged amino acids. This amphiphilic property of melittin has resulted in melittin being used as a suitable model peptide for monitoring lipid–protein interactions in membranes. In this review, the solution and membrane properties of melittin are highlighted, with an emphasis on melittin–membrane interaction using biophysical approaches. The recent applications of melittin in various cellular processes are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

DTPC:

1,2–ditetradecyl-sn-glycero-3-phosphocholine

DMPC:

1,2-dimyristoyl-sn-glycero-3-phosphocholine

DLPC:

1,2-dilauroyl-sn-glycero-3-phosphocholine

DPhPC:

1,2-diphytanoyl-sn-glycero-3-phosphocholine

DOPA:

1,2-dioleoyl-sn-glycero-3-phosphoacid

DOPC:

1,2-dioleoyl-sn-glycero-3-phosphocholine

PC:

Phosphatidylcholine

PG:

Phosphatidylglycerol

PEI:

Poly(ethyleneimine)

POPG:

1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol

REES:

Red edge excitation shift

References

  • Allende D, McIntosh TJ (2003) Lipopolysaccharides in bacterial membranes act like cholesterol in eukaryotic plasma membranes in providing protection against melittin-induced bilayer lysis. Biochemistry 42:1101–1108

    PubMed  CAS  Google Scholar 

  • Allende D, Vidal A, Simon SA, McIntosh TJ (2003) Bilayer interfacial properties modulate the binding of amphipathic peptides. Chem Phys Lipids 122:65–76

    PubMed  CAS  Google Scholar 

  • Allende D, Simon SA, McIntosh TJ (2005) Melittin-induced bilayer leakage depends on lipid material properties: evidence for toroidal pores. Biophys J 88:1828–1837

    PubMed  CAS  Google Scholar 

  • Altenbach C, Hubbell WL (1988) The aggregation state of spin-labeled melittin in solution and bound to phospholipid membranes: evidence that membrane-bound melittin is monomeric. Proteins 3:230–242

    PubMed  CAS  Google Scholar 

  • Anderson D, Terwilliger RC, Wickner W, Eisenberg D (1980) Melittin forms crystals which are suitable for high resolution X-ray structural analysis and which reveal a molecular 2-fold axis of symmetry. J Biol Chem 255:2578–2582

    PubMed  CAS  Google Scholar 

  • Asthana N, Yadav SP, Ghosh JK (2004) Dissection of antibacterial and toxic activity of melittin: a leucine zipper motif plays a crucial role in determining its hemolytic activity but not antibacterial activity. J Biol Chem 279:55042–55050

    PubMed  CAS  Google Scholar 

  • Bachar M, Becker OM (2000) Protein-induced membrane disorder: a molecular dynamics study of melittin in a dipalmitoylphosphatidylcholine bilayer. Biophys J 78:1359–1375

    PubMed  CAS  Google Scholar 

  • Baker KJ, East JM, Lee AG (1995) Mechanism of inhibition of the Ca2+-ATPase by melittin. Biochemistry 34:3596–3604

    PubMed  CAS  Google Scholar 

  • Banemann A, Deppisch H, Gross R (1998) The lipopolysaccharide of Bordetella bronchiseptica acts as a protective shield against antimicrobial peptides. Infect Immun 66:5607–5612

    PubMed  CAS  Google Scholar 

  • Banks BEC, Dempsey CE, Pearce FL, Vernon CA, Wholley TE (1981) New methods of isolating been venom peptides. Anal Biochem 116:48–52

    PubMed  CAS  Google Scholar 

  • Barnham KJ, Monks SA, Hinds MG, Azad AA, Norton RS (1997) Solution structure of a polypeptide from the N-terminus of the HIV protein Nef. Biochemistry 36:5970–5980

    PubMed  CAS  Google Scholar 

  • Batenburg AM, Hibbeln JC, de Kruijff B (1987) Lipid specific penetration of melittin into phospholipid model membranes. Biochim Biophys Acta 903:155–165

    PubMed  CAS  Google Scholar 

  • Batenburg AM, van Esch JH, de Kruijff B (1988) Melittin-induced changes of the macroscopic structure of phosphatidylethanolamines. Biochemistry 27:2324–2331

    PubMed  CAS  Google Scholar 

  • Baumann G, Mueller P (1974) A molecular model of membrane excitability. J Supramol Struct 2:538–557

    PubMed  CAS  Google Scholar 

  • Bazzo R, Tappin MJ, Pastore A, Harvey TS, Carver JA, Campbell ID (1988) The structure of melittin. A 1H-NMR study in methanol. Eur J Biochem 173:139–146

    PubMed  CAS  Google Scholar 

  • Bechinger B (1997) Structure and functions of channel-forming peptides: magainins, cecropins, melittin and alamethicin. J Membr Biol 156:197–211

    PubMed  CAS  Google Scholar 

  • Bechinger B (1999) The structure, dynamics and orientation of antimicrobial peptides in membranes by solid-state NMR spectroscopy. Biochim Biophys Acta 1462:157–183

    PubMed  CAS  Google Scholar 

  • Bechinger B (2004) Structure and function of membrane-lytic peptides. Crit Rev Plant Sci 23:271–292

    CAS  Google Scholar 

  • Bello J, Bello HR, Granados E (1982) Conformation and aggregation of melittin: dependence of pH and concentration. Biochemistry 21:461–465

    PubMed  CAS  Google Scholar 

  • Benachir T, Lafleur M (1995) Study of vesicle leakage induced by melittin. Biochim Biophys Acta 1235:452–460

    PubMed  Google Scholar 

  • Benachir T, Lafleur M (1996) Osmotic and pH transmembrane gradients control the lytic power of melittin. Biophys J 70:831–840

    PubMed  CAS  Google Scholar 

  • Benachir T, Monette M, Grenier J, Lafleur M (1997) Melittin-induced leakage from phosphatidylcholine vesicles is modulated by cholesterol: a property used for membrane targeting. Eur Biophys J 25:201–210

    CAS  Google Scholar 

  • Bernard E, Faucon JF, Dufourcq J (1982) Phase separation induced by melittin in negatively charged phospholipid bilayers as detected by fluorescence polarization and differential scanning calorimetry. Biochim Biophys Acta 688:152–162

    PubMed  CAS  Google Scholar 

  • Bernèche S, Nina M, Roux B (1998) Molecular dynamics simulation of melittin in a dimyristoylphosphatidylcholine bilayer membrane. Biophys J 75:1603–1618

    PubMed  Google Scholar 

  • Bernheimer AW, Ruby B (1986) Interactions between membranes and cytolytic peptides. Biochim Biophys Acta 864:123–141

    PubMed  CAS  Google Scholar 

  • Beschiaschvili G, Baeuerle HD (1991) Effective charge of melittin upon interaction with POPC vesicles. Biochim Biophys Acta 1068:195–200

    PubMed  CAS  Google Scholar 

  • Beschiaschvili G, Seelig J (1990) Melittin binding to mixed phosphatidylglycerol/phosphatidylcholine membranes. Biochemistry 29:52–58

    PubMed  CAS  Google Scholar 

  • Bettinger T, Carlisle RC, Read ML, Ogris M, Seymour LW (2001) Peptide-mediated RNA delivery: a novel approach for enhanced transfection of primary and post-mitotic cells. Nucleic Acids Res 29:3882–3891

    PubMed  CAS  Google Scholar 

  • Bismuto E, Sirangelo I, Irace G (1993) Folding and dynamics of melittin in reversed micelles. Biochim Biophys Acta 1146:213–218

    PubMed  CAS  Google Scholar 

  • Blondelle SE, Houghten RA (1991a) Hemolytic and antimicrobial activities of twenty-four individual omission analogues of melittin. Biochemistry 30:4671–4678

    CAS  Google Scholar 

  • Blondelle SE, Houghten RA (1991b) Probing the relationships between the structure and hemolytic activity of melittin with a complete set of leucine substitution analogs. Pept Res 4:12–18

    CAS  Google Scholar 

  • Blondelle SE, Simpkins LR, Pérez-Payá E, Houghten RA (1993) Influence of tryptophan residues on melittin’s hemolytic activity. Biochim Biophys Acta 1202:331–336

    PubMed  CAS  Google Scholar 

  • Bos JL (1989) ras oncogenes in human cancer: a review. Cancer Res 49:4682–4689

    PubMed  CAS  Google Scholar 

  • Bos JL, Fearon ER, Hamilton SR, Verlaan-de Vries M, van Boom JH, van der Eb AJ, Vogelstein B (1987) Prevalence of ras gene mutations in human colorectal cancers. Nature 327:293–297

    PubMed  CAS  Google Scholar 

  • Bradrick TD, Georghiou S (1987) Kinetics of melittin-induced fusion of dipalmitoylphosphatidylcholine small unilamellar vesicles. Biochim Biophys Acta 905:494–498

    PubMed  CAS  Google Scholar 

  • Bradrick TD, Freire E, Georghiou S (1989) A high-sensitivity differential scanning calorimetric study of the interaction of melittin with dipalmitoylphosphatidylcholine fused unilamellar vesicles. Biochim Biophys Acta 982:94–102

    PubMed  CAS  Google Scholar 

  • Bradrick TD, Philippetis A, Georghiou S (1995) Stopped-flow fluorometric study of the interaction of melittin with phospholipid bilayers: importance of the physical state of the bilayer and the acyl chain length. Biophys J 69:1999–2010

    PubMed  CAS  Google Scholar 

  • Bradshaw JP, Dempsey CE, Watts A (1994) A combined X-ray and neutron diffraction study of selectively deuterated melittin in phospholipid bilayers: effect of pH. Mol Membr Biol 11:79–86

    Article  PubMed  CAS  Google Scholar 

  • Brauner JW, Mendelsohn R, Prendergast FG (1987) Attenueted total reflectance Fourier transform infrared studies of the interaction of melittin, two fragments of melittin, and δ-hemolysin with phosphatidylcholines. Biochemistry 26:8151–8158

    PubMed  CAS  Google Scholar 

  • Brown LR, Wüthrich K (1981) Melittin bound to dodecylphosphocholine micelles. H-NMR assignments and global conformational features. Biochim Biophys Acta 647:95–111

    PubMed  CAS  Google Scholar 

  • Brown LR, Lauterwein J, Wüthrich K (1980) High-resolution 1H-NMR studies of self-aggregation of melittin in aqueous solution. Biochim Biophys Acta 622:231–244

    PubMed  CAS  Google Scholar 

  • Brown LR, Brawn W, Kumar A, Wüthrich K (1982) High resolution nuclear magnetic resonance studies of the conformation and orientation of melittin bound to a lipid–water interface. Biophys J 37:319–328

    PubMed  CAS  Google Scholar 

  • Cajal Y, Jain MK (1997) Synergism between mellitin and phospholipase A2 from bee venom: apparent activation by intervesicle exchange of phospholipids. Biochemistry 36:3882–3893

    PubMed  CAS  Google Scholar 

  • Castano S, Cornut I, Buttner K, Dasseux JL, Dufourcq J (1999) The amphipathic helix concept: length effects on ideally amphipathic L i K j (i=2j) peptides to acquire optimal hemolytic activity. Biochim Biophys Acta 1416:161–175

    PubMed  CAS  Google Scholar 

  • Chandani B, Balasubramanian D (1986) Analysis of the interaction of membrane-active peptides with membranes: the case of melittin in surfactant assemblies. Biopolymers 25:1259–1272

    CAS  Google Scholar 

  • Chattopadhyay A (2003) Exploring membrane organization and dynamics by the wavelength-selective fluorescence approach. Chem Phys Lipids 122:3–17

    PubMed  CAS  Google Scholar 

  • Chattopadhyay A, London E (1987) Parallax method for direct measurement of membrane penetration depth utilizing fluorescence quenching by spin-labeled phospholipids. Biochemistry 26:39–45

    PubMed  CAS  Google Scholar 

  • Chattopadhyay A, Rukmini R (1993) Restricted mobility of the sole tryptophan in membrane-bound melittin. FEBS Lett 335:341–344

    PubMed  CAS  Google Scholar 

  • Chicharro C, Granata C, Lozano R, Andreu D, Rivas L (2001) N-terminal fatty acid substitution increases the leishmanicidal activity of CA(1–7)M(2–9), a cecropin–melittin hybrid peptide. Antimicrob Agents Chemother 45:2441–2449

    PubMed  CAS  Google Scholar 

  • Christian AE, Haynes MP, Phillips MC, Rothblat GH (1997) Use of cyclodextrins for manipulating cellular cholesterol content. J Lipid Res 38:2264–2272

    PubMed  CAS  Google Scholar 

  • Clague MJ, Cherry RJ (1988) Comparison of p25 presequence peptide and melittin. Red blood cell haemolysis and band 3 aggregation. Biochem J 252:791–794

    PubMed  CAS  Google Scholar 

  • Constantinescu I, Lafleur M (2004) Influence of the lipid composition on the kinetics of concerted insertion and folding of melittin in bilayers. Biochim Biophys Acta 1667:26–37

    PubMed  CAS  Google Scholar 

  • Cserhati T, Szogyi M (1994) Interaction of phospholipids with proteins and peptides. New advances IV. Int J Biochem 26:1–18

    PubMed  CAS  Google Scholar 

  • Cuppoletti J (1990) [125I]azidosalicylyl melittin binding domains: evidence for a polypeptide receptor on the gastric (H+ K+)ATPase. Arch Biochem Biophys 278:409–415

    PubMed  CAS  Google Scholar 

  • Cuppoletti J, Blumenthal KE, Malinowska DH (1989) Melittin inhibition of the gastric (H+ + K+) ATPase and photoaffinity labeling with [125I]azidosalicylyl melittin. Arch Biochem Biophys 275:263–270

    PubMed  CAS  Google Scholar 

  • Cuppoletti J, Abbott AJ (1990) Interaction of melittin with the (Na+ + K+)ATPase: evidence for a melittin-induced conformational change. Arch Biochem Biophys 283:249–257

    PubMed  CAS  Google Scholar 

  • Dasseux JL, Faucon JF, Lafleur M, Pezolet M, Dufourcq J (1984) A restatement of melittin-induced effects on the thermotropism of zwitterionic phospholipids. Biochim Biophys Acta 775:37–50

    PubMed  CAS  Google Scholar 

  • 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 1462:71–87

    PubMed  CAS  Google Scholar 

  • Dawson CR, Drake AF, Helliwell J, Hider RC (1978) The interaction of bee melittin with lipid bilayer membranes. Biochim Biophys Acta 510:75–86

    PubMed  CAS  Google Scholar 

  • de Kruijff B (1990) Cholesterol as a target for toxins. Biosci Rep 10:127–130

    PubMed  Google Scholar 

  • DeGrado WF, Kezdy FJ, Kaiser ET (1981) Design, synthesis, and characterization of a cytotoxic peptide with melittin-like activity. J Am Chem Soc 103:679–681

    CAS  Google Scholar 

  • DeGrado WF, Musso GF, Lieber M, Kaiser ET, Kezdy FJ (1982) Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue. Biophys J 37:329–338

    PubMed  CAS  Google Scholar 

  • Demchenko AP (1988) Red-edge-excitation fluorescence spectroscopy of single-tryptophan proteins. Eur Biophys J 16:121–129

    PubMed  CAS  Google Scholar 

  • Demchenko AP (2002) The red-edge effects: 30 years of exploration. Luminescence 17:19–42

    PubMed  CAS  Google Scholar 

  • Dempsey CE (1988) pH-dependence of hydrogen-exchange from backbone peptide amides of melittin in methanol. Biochemistry 27:6893–6901

    CAS  Google Scholar 

  • Dempsey CE (1990) The actions of melittin on membranes. Biochim Biophys Acta 1031:143–161

    PubMed  CAS  Google Scholar 

  • Dempsey CE (1992) Quantitation of the effects of an internal proline residue on individual hydrogen bond stabilities in an alpha-helix: pH-dependent amide exchange in melittin and [Ala-14]melittin. Biochemistry 31:4705–4712

    PubMed  CAS  Google Scholar 

  • Dempsey CE, Watts A (1987) A deuterium and phosphorus-31 nuclear magnetic resonance study of the interaction of melittin with dimyristoylphosphatidylcholine bilayers and the effects of contaminating phospholipase A2. Biochemistry 26:5803–5811

    PubMed  CAS  Google Scholar 

  • Dempsey CE, Sternberg B (1991) Reversible disc-micellization of dimyristoylphosphatidylcholine bilayers induced by melittin and [Ala-14]melittin. Biochim Biophys Acta 1061:175–184

    PubMed  CAS  Google Scholar 

  • Dempsey CE, Bazzo R, Harvey TS, Syperek I, Boheim G, Campbell ID (1991) Contribution of proline-14 to the structure and actions of melittin. FEBS Lett 281:240–244

    PubMed  CAS  Google Scholar 

  • Dempsey CE, Butler GS (1992) Helical structure and orientation of melittin in dispersed phospholipid membranes from amide exchange analysis in situ. Biochemistry 31:11973–11977

    PubMed  CAS  Google Scholar 

  • Diaz-Achirica P, Ubach J, Guinea A, Andreu D, Rivas L (1998) The plasma membrane of Leishmania donovani promastigotes is the main target for CA(1–8)M(1–18), a synthetic cecropin A–melittin hybrid peptide. Biochem J 330:453–460

    PubMed  CAS  Google Scholar 

  • Dufourcq J, Dasseux JL, Faucon JF (1984) In: Alouf JE, Fehrenbach FJ, Freer JH, Jeljaszewicz J (eds) Bacterial protein toxins. Academic Press, London, pp 127–138

  • Dufourcq J, Faucon JF, Fourche G, Dasseux JL, Le Maire M, Gulik-Krzywicki T (1986) Morphological changes of phosphatidylcholine bilayers induced by melittin: vesicularization, fusion, discoidal particles. Biochim Biophys Acta 859:33–48

    PubMed  CAS  Google Scholar 

  • Dufourc EJ, Smith ICP, Dufourcq J (1986) Molecular details of melittin-induced lysis of phospholipid membranes as revealed by deuterium and phosphorus NMR. Biochemistry 25:6448–6455

    PubMed  CAS  Google Scholar 

  • Dufton MJ, Hider RC, Cherry RJ (1984) The influence of melittin on the rotation of band 3 protein in the human erythrocyte membrane. Eur Biophys J 11:17–24

    PubMed  CAS  Google Scholar 

  • Eisenberg D, Wesson M (1990) The most highly amphiphilic alpha-helices include two amino acid segments in human immunodeficiency virus glycoprotein 41. Biopolymers 29:171–177

    PubMed  CAS  Google Scholar 

  • El Jastimi R, Lafleur M (1999) A dual-probe fluorescence method to examine selective perturbations of membrane permeability by melittin. Biospectroscopy 5:133–140

    PubMed  CAS  Google Scholar 

  • Epand RM, Vogel HJ (1999) Diversity of antimicrobial peptides and their mechanisms of action. Biochim Biophys Acta 1462:11–28

    PubMed  CAS  Google Scholar 

  • Essen LO, Siegert R, Lehmann WD, Oesterhelt D (1998) Lipid patches in membrane protein oligomers: crystal structure of the bacteriorhodopsin–lipid complex. Proc Natl Acad Sci USA 95:11673–11678

    PubMed  CAS  Google Scholar 

  • Faucon JF, Dufourcq I, Lussan C (1979) The self-association of melittin and its binding to lipids: an intrinsic fluorescence polarization study. FEBS Lett 102:187–190

    PubMed  CAS  Google Scholar 

  • Faucon JF, Bonmatin JM, Dufourcq J, Dufourc EJ (1995) Acyl chain length dependence in the stability of melittin–phosphatidylcholine complexes. A light scattering and 31P-NMR study. Biochim Biophys Acta 1234:235–243

    PubMed  Google Scholar 

  • Fletcher JE, Jiang MS (1993) Possible mechanisms of action of cobra snake venom cardiotoxins and bee venom melittin. Toxicon 31:669–695

    PubMed  CAS  Google Scholar 

  • Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M (1987) Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature 327:298–303

    PubMed  CAS  Google Scholar 

  • Frey S, Tamm LK (1991) Orientation of melittin in phospholipid bilayers. A polarized attenuated total reflection infrared study. Biophys J 60:922–930

    PubMed  CAS  Google Scholar 

  • Fukushima N, Kohno M, Kato T, Kawamoto S, Okuda K, Misu Y, Ueda H (1998) Melittin, a metabostatic peptide inhibiting Gs activity. Peptides 19:811–819

    PubMed  CAS  Google Scholar 

  • Fung LK, Stryer L (1978) Surface density determination in membranes by fluorescence energy transfer. Biochemistry 17:5241–5248

    PubMed  CAS  Google Scholar 

  • Garnier J, Gaye P, Mercier JC, Robson B (1980) Structural properties of signal peptides and their membrane insertion. Biochimie 62:231–239

    CAS  PubMed  Google Scholar 

  • Georghiou S, Thompson M, Mukhopadhyay AK (1982) Melittin–phospholipid interaction studied by employing the single tryptophan residue as an intrinsic fluorescent probe. Biochim Biophys Acta 688:441–452

    PubMed  CAS  Google Scholar 

  • Gevod VS, Birdi KS (1984) Melittin and the 8–26 fragment. Differences in ionophoric properties as measured by monolayer method. Biophys J 45:1079–1083

    PubMed  CAS  Google Scholar 

  • Ghosh AK, Rukmini R, Chattopadhyay A (1997) Modulation of tryptophan environment in membrane-bound melittin by negatively charged phospholipids: implications in membrane organization and function. Biochemistry 36:14291–14305

    PubMed  CAS  Google Scholar 

  • Golding C, O’Shea P (1995) The interactions of signal sequences with membranes. Biochem Soc Trans 23:971–976

    PubMed  CAS  Google Scholar 

  • Gómara MJ, Nir S, Nieva JL (2003) Effects of sphingomyelin on melittin pore formation. Biochim Biophys Acta 1612:83–89

    PubMed  Google Scholar 

  • Gorbenko G, Handa T, Saito H, Molotkovsky J, Tanaka M, Egashira M, Nakano M (2003) Effect of cholesterol on bilayer location of the class A peptide Ac-18A-NH2 as revealed by fluorescence resonance energy transfer. Eur Biophys J 32:703–709

    PubMed  CAS  Google Scholar 

  • Gromova IA, Molokovsky JG, Bergelson LD (1992) Anthrylvinyl-labeled phospholipids as fluorescent membrane probes. The action of melittin on multilipid systems. Chem Phys Lipids 60:235–246

    PubMed  CAS  Google Scholar 

  • Guz A, Wasylewski Z (1994) Red-edge excitation fluorescence spectroscopy of proteins in reversed micelles. Red-edge excitation fluorescence spectroscopy of proteins in reversed micelles. J Protein Chem 13:393–399

    PubMed  CAS  Google Scholar 

  • Habermann E (1972) Bee and wasp venoms. Science 177:314–322

    PubMed  CAS  Google Scholar 

  • Habermann E, Kowallek H (1970) Modifications of amino group and tryptophan in melittin as an aid to recognition of structure–activity relationships. Hoppe-Seyler’s Z Physiol Chem 351:884–890

    PubMed  CAS  Google Scholar 

  • Hanke W, Methfessel C, Wilmsen HU, Katz E, Jung G, Boheim G (1983) Melittin and a chemically modified trichotoxin form alamethicin-type multi-state pores. Biochim Biophys Acta 727:108–114

    PubMed  CAS  Google Scholar 

  • Hermetter A, Lakowicz JR (1986) The aggregation state of mellitin in lipid bilayers. An energy transfer study. J Biol Chem 261:8243–8248

    PubMed  CAS  Google Scholar 

  • Herwaldt BL (1999) Leishmaniasis. Lancet 354:1191–1199

    PubMed  CAS  Google Scholar 

  • Hider RC, Khader F, Tatham AS (1983) Lytic activity of monomeric and oligomeric melittin. Biochim Biophys Acta 728:206–214

    PubMed  CAS  Google Scholar 

  • Higashijima T, Uzu S, Nakajima T, Ross EM (1988) Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins). J Biol Chem 263:6491–6494

    PubMed  CAS  Google Scholar 

  • Higashijima T, Burnier J, Ross EM (1990) Regulation of Gi and Go by mastoparan, related amphiphilic peptides, and hydrophobic amines. Mechanism and structural determinants of activity. J Biol Chem 265:14176–14186

    PubMed  CAS  Google Scholar 

  • Hincha DK, Crowe JH (1996) The lytic activity of the bee venom peptide melittin is strongly reduced by the presence of negatively charged phospholipids or chloroplast galactolipids in the membranes of phosphatidylcholines large unilamellar vesicles. Biochim Biophys Acta 1284:162–170

    PubMed  Google Scholar 

  • Ho C, Stubbs CD (1992) Hydration at the membrane protein–lipid interface. Biophys J 63:897–902

    PubMed  CAS  Google Scholar 

  • Hristova K, Dempsey CE, White SH (2001) Structure, location, and lipid perturbations of melittin at the membrane interface. Biophys J 80:801–811

    PubMed  CAS  Google Scholar 

  • Hu K-S, Dufton MJ, Morrison I, Cherry RJ (1985) Protein rotational diffusion measurements on the interaction of bee venom melittin with bacteriorhodopsin in lipid vesicles. Biochim Biophys Acta 816:358–364

    PubMed  CAS  Google Scholar 

  • Huang HW (2000) Action of antimicrobial peptides: two-state model. Biochemistry 39:8347–8352

    PubMed  CAS  Google Scholar 

  • Hui SW, Stewart CM, Cherry RJ (1990) Electron microscopic observation of the aggregation of membrane proteins in human erythrocyte by melittin. Biochim Biophys Acta 1023:335–340

    PubMed  CAS  Google Scholar 

  • Hung WC, Lee MT (2006) The interaction of melittin with E. coli membrane: the role of cardiolipin. Chinese J Phys 44:137–149

    CAS  Google Scholar 

  • Ikura T, Go N, Inagaki F (1991) Refined structure of melittin bound to perdeuterated dodecylphosphocholine micelles as studied by 2D-NMR and distance geometry calculation. Proteins 9:81–89

    PubMed  CAS  Google Scholar 

  • Inagaki F, Shimada I, Kawaguchi K, Hirano M, Terasawa I, Ikura T, Go N (1989) Structure of melittin bound to perdeuterated dodecylphosphocholine micelles as studied by two-dimensional NMR and distance geometry calculations. Biochemistry 28:5985–5991

    CAS  Google Scholar 

  • Iwadate M, Asakura T, Williamson MP (1998) The structure of the melittin tetramer at different temperatures. An NOE-based calculation with chemical shift refinement. Eur J Biochem 257:479–487

    PubMed  CAS  Google Scholar 

  • John E, Jähnig F (1988) Dynamics of melittin in water and membranes as determined by fluorescence anisotropy decay. Biophys J 54:817–827

    PubMed  CAS  Google Scholar 

  • John E, Jähnig F (1991) Aggregation state of melittin in lipid vesicle membranes. Biophys J 60:319–328

    CAS  PubMed  Google Scholar 

  • Juvvadi P, Vumman S, Merrifield RB (1996) Synthetic melittin, its enantio, retro, and retroenantio isomers, and selected chimeric analogs: their antibacterial, hemolytic, and lipid bilayer action. J Am Chem Soc 118:8989–8997

    CAS  Google Scholar 

  • Kaiser ET, Kezdy FJ (1983) Secondary structures of proteins and peptides in amphiphilic environment. Proc Natl Acad Sci USA 80:1137–1143

    PubMed  CAS  Google Scholar 

  • Kaiser ET, Kezdy FJ (1984) Amphiphilic secondary structure: design of peptide hormones. Science 223:249–255

    PubMed  CAS  Google Scholar 

  • Kaszycki P, Wasylewski Z (1990) Fluorescence-quenching-resolved spectra of melittin in lipid bilayers. Biochim Biophys Acta 1040:337–345

    PubMed  CAS  Google Scholar 

  • Katsu T, Ninomiya C, Kuroko M, Kobayashi H, Hirota T, Fujita Y (1988) Action mechanism of amphipathic peptides gramicidin S and melittin on erythrocyte membrane. Biochim Biophys Acta 939:57–63

    PubMed  CAS  Google Scholar 

  • Kempf C, Klausner RD, Weinstein JN, Renswoude JV, Pincus M, Blumenthal R (1982) Voltage-dependent trans-bilayer orientation of melittin. J Biol Chem 257:2469–2476

    PubMed  CAS  Google Scholar 

  • Kleinschmidt JH, Mahaney JE, Thomas DD, Marsh D (1997) Interaction of bee venom melittin with zwitterionic and negatively charged phospholipid bilayers: a spin-label electron spin resonance study. Biophys J 72:767–778

    PubMed  CAS  Google Scholar 

  • Knoppel E, Eisenberg D, Wickner W (1979) Interactions of melittin, a preprotein model, with detergents. Biochemistry 18:4177–4181

    PubMed  CAS  Google Scholar 

  • Kourie JI, Shorthouse AA (2000) Properties of cytotoxic peptide-formed ion channels. Am J Physiol Cell Physiol 278:C1063–C1087

    PubMed  CAS  Google Scholar 

  • Kouyama T, Nishikawa T, Tokuhisa T, Okumura H (2004) Crystal structure of the L intermediate of bacteriorhodopsin: evidence for vertical translocation of a water molecule during the proton pumping cycle. J Mol Biol 335:531–546

    PubMed  CAS  Google Scholar 

  • Kriech MA, Conboy JC (2003) Label-free chiral detection of melittin binding to a membrane. J Am Chem Soc 125:1148–1149

    PubMed  CAS  Google Scholar 

  • Kuchinka E, Seelig J (1989) Interaction of melittin with phosphatidylcholine membranes. Binding isotherm and lipid head-group conformation. Biochemistry 28:4216–4221

    PubMed  CAS  Google Scholar 

  • Ladokhin AS, Selsted ME, White SH (1997) Sizing membrane pores in lipid vesicles by leakage of co-encapsulated markers: pore formation by melittin. Biophys J 72:1762–1766

    PubMed  CAS  Google Scholar 

  • Ladokhin AS, White SH (1999) Folding of amphipathic alpha-helices on membranes: energetics of helix formation by melittin. J Mol Biol 285:1363–1369

    PubMed  CAS  Google Scholar 

  • Ladokhin AS, White SH (2001) ‘Detergent-like’ permeabilization of anionic lipid vesicles by melittin. Biochim Biophys Acta 1514:253–260

    PubMed  CAS  Google Scholar 

  • Lam YH, Wassall SR, Morton CJ, Smith R, Separovic F (2001) Solid-state NMR structure determination of melittin in a lipid environment. Biophys J 81:2752–2761

    PubMed  CAS  Google Scholar 

  • Lauterwein J, Bosch C, Brown LR, Wuthrich K (1979) Physicochemical studies of the protein–lipid interactions in melittin-containing micelles. Biochim Biophys Acta 556:244–264

    PubMed  CAS  Google Scholar 

  • Lauterwein J, Brown LR, Wüthrich K (1980) High-resolution 1H-NMR studies of monomeric melittin in aqueous solution. Biochim Biophys Acta 622:219–230

    PubMed  CAS  Google Scholar 

  • Lavignac N, Lazenby M, Franchini J, Ferruti P, Duncan R (2005) Synthesis and preliminary evaluation of poly(amidoamine)-melittin conjugates as endosomolytic polymers and/or potential anticancer therapeutics. Int J Pharm 300:102–112

    PubMed  CAS  Google Scholar 

  • Lazarev VN, Parfenova TM, Gularyan SK, Misyurina O Yu, Akopian TA, Govorun VM (2002) Induced expression of melittin, an antimicrobial peptide, inhibits infection by Chlamydia trachomatis and Mycoplasma hominis in a HeLa cell line. Int J Antimicrob Agents 19:133–137

  • Lazaridis T (2003) Effective energy function for proteins in lipid membranes. Proteins 52:176–192

    PubMed  CAS  Google Scholar 

  • Lee TH, Mozsolits H, Aguilar MI (2001) Measurement of the affinity of melittin for zwitterionic and anionic membranes using immobilized lipid biosensors. J Pept Res 58:464–476

    PubMed  CAS  Google Scholar 

  • Leippe M, Ebel S, Schoenberger OL, Horstmann RD, Muller-Eberhard HJ (1991) Pore-forming peptide of pathogenic Entamoeba histolytica. Proc Natl Acad Sci USA 88:7659–7663

    PubMed  CAS  Google Scholar 

  • Leippe M, Tannich E, Nickel R, van der Goot G, Pattus F, Horstmann RD, Müller-Eberhard HJ (1992) Primary and secondary structure of the pore-forming peptide of pathogenic Entamoeba histolytica. EMBO J 11:3501–3506

    PubMed  CAS  Google Scholar 

  • Lin JH, Baumgaertner A (2000) Stability of a melittin pore in a lipid bilayer: a molecular dynamics study. Biophys J 78:1714–1724

    PubMed  CAS  Google Scholar 

  • Liscum L, Underwood KW (1995) Intracellular cholesterol transport and compartmentation. J Biol Chem 270:15443–15446

    PubMed  CAS  Google Scholar 

  • Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35:13723–13728

    PubMed  CAS  Google Scholar 

  • Luisi PL, Magid LJ (1986) Solubilization of enzymes and nucleic acids in hydrocarbon micellar solutions. CRC Crit Rev Biochem 20:409–474

    PubMed  CAS  Google Scholar 

  • Luisi PL, Giomini M, Pileni MP, Robinson BH (1988) Reverse micelles as hosts for proteins and small molecules. Biochim Biophys Acta 947:209–246

    PubMed  CAS  Google Scholar 

  • Luque-Ortega JR, Saugar JM, Chiva C, Andreu D, Rivas L (2003) Identification of new leishmanicidal peptide lead structures by automated real-time monitoring of changes in intracellular ATP. Biochem J 375:221–230

    PubMed  CAS  Google Scholar 

  • Mahaney JE, Thomas DD (1991) Effects of melittin on molecular dynamics and Ca-ATPase activity in sarcoplasmic reticulum membranes: electron paramagnetic resonance. Biochemistry 30:7171–7180

    PubMed  CAS  Google Scholar 

  • Mahaney JE, Kleinschmidt J, Marsh D, Thomas DD (1992) Effects of melittin on lipid–protein interactions in sarcoplasmic reticulum membranes. Biophys J 63:1513–1522

    PubMed  CAS  Google Scholar 

  • Maloy WL, Kari UP (1995) Structure–activity studies on magainins and other host defense peptides. Biopolymers 37:105–122

    PubMed  CAS  Google Scholar 

  • Marcos JF, Beachy RN, Houghten RA, Blondelle SE, Pérez-Payá E (1995) Inhibition of a plant virus infection by analogs of melittin. Proc Natl Acad Sci USA 92:12466–12469

    PubMed  CAS  Google Scholar 

  • Matsuzaki K, Murase O, Tokuda H, Fujii N, Miyajima K (1996) Physicochemical determinants for the interactions of magainins 1 and 2 with acidic lipid bilayers. Biochim Biophys Acta 1063:162–170

    Google Scholar 

  • Matsuzaki K, Murase O, Tokuda H, Funakoshi S, Fujii N, Miyajima K (1994) Orientational and aggregational states of magainin 2 in phospholipid bilayers. Biochemistry 33:3342–3349

    PubMed  CAS  Google Scholar 

  • Matsuzaki K, Yoneyama S, Miyajima K (1997) Pore formation and translocation of melittin. Biophys J 73:831–838

    PubMed  CAS  Google Scholar 

  • Maurer T, Lucke C, Ruterjans H (1991) Investigation of the membrane-active peptides melittin and glucagons by photochemically induced dynamic-nuclear-polarization (photo-CIDNP) NMR. Eur J Biochem 196:135–141

    PubMed  CAS  Google Scholar 

  • McAuley KE, Fyfe PK, Ridge JP, Isaacs NW, Cogdell RJ, Jones MR (1999) Structural details of an interaction between cardiolipin and an integral membrane protein. Proc Natl Acad Sci USA 96:14706–14711

    PubMed  CAS  Google Scholar 

  • Merrifield RB, Juvvadi P, Andreu D, Ubach J, Boman A, Boman HG (1995) Retro and retroenantio analogs of cecropin–melittin hybrids. Proc Natl Acad Sci USA 92:3449–3453

    PubMed  CAS  Google Scholar 

  • Mitchell DC Litman BJ (1998) Effect of cholesterol on molecular order and dynamics in highly polyunsaturated phospholipid bilayers. Biophys J 75:896–908

    Google Scholar 

  • Monette M, Lafleur M (1995) Modulation of melittin-induced lysis by surface charge density of membranes. Biophys J 68:187–195

    PubMed  CAS  Google Scholar 

  • Monette M, Lafleur M (1996) Influence of lipid chain unsaturation on melittin-induced micellization. Biophys J 70:2195–2202

    PubMed  CAS  Google Scholar 

  • Monette M, van Calsteren MR, Lafleur M (1993) Effect of cholesterol on the polymorphism of dipalmitoylphosphatidylcholine/melittin complexes: an NMR study. Biochim Biophys Acta 1149:319–328

    PubMed  CAS  Google Scholar 

  • Morgan CG, Williamson H, Fuller S, Hudson B (1983) Melittin induces fusion of unilamellar phospholipid vesicles. Biochim Biophys Acta 732:668–674

    PubMed  CAS  Google Scholar 

  • Morii H, Honda S, Ohashi S, Uedaira H (1994) Alpha-helical assembly of biologically active peptides and designed helix bundle protein. Biopolymers 34:481–488

    PubMed  CAS  Google Scholar 

  • Mozsolits H, Wirth HJ, Werkmeister J, Aguilar MI (2001) Analysis of antimicrobial peptide interactions with hybrid bilayer membrane systems using surface plasmon resonance. Biochim Biophys Acta 1512:64–76

    PubMed  CAS  Google Scholar 

  • Mukherjee S, Zha X, Tabas I, Maxfield FR (1998) Cholesterol distribution in living cells: fluorescence imaging using dehydroergosterol as a fluorescent cholesterol analog. Biophys J 75:1915–1925

    PubMed  CAS  Google Scholar 

  • Naito A, Nagao T, Norisada K, Mizuno T, Tuzi S, Saitô H (2000) Conformation and dynamics of melittin bound to magnetically oriented lipid bilayers by solid-state 31P and 13C NMR spectroscopy. Biophys J 78:2405–2417

    PubMed  CAS  Google Scholar 

  • Needham D (1995) Cohesion and permeability in lipid bilayer vesicles. In: Simon SA, Disalvo EA (eds) Permeability and stability of bilayers. CRC Press, Boca Raton, Florida, pp 49–76

    Google Scholar 

  • Neumann W, Habermann E, Hansen H (1953) Differentiation of two hemolytic factors in bee venom. Naunyn-Schmiedebergs Arch Exp Path Pharma 217:130–143

    CAS  Google Scholar 

  • Niemz A, Tirrel DA (2001) Self-association and membrane-binding behavior of melittins containing trifluoroleucine. J Am Chem Soc 123:7407–7413

    PubMed  CAS  Google Scholar 

  • Nir S, Nieva JL (2000) Interactions of peptides with liposomes: pore formation and fusion. Prog Lipid Res 39:181–206

    PubMed  CAS  Google Scholar 

  • Nishiya T, Chou HL (1991) The study of lipid–protein interactions: effect of melittin on phase transition of phosphatidylethanolamine and sensitivity of phospholipases to phase state. J Biochem 110:732–736

    PubMed  CAS  Google Scholar 

  • Niu W, Wu Y, Sui SF (2000) Orientation of membrane-bound melittin studied by a combination of HPLC and liquid secondary ion mass spectrometry (LSIMS). IUBMB Life 50:215–219

    PubMed  CAS  Google Scholar 

  • Ogris M, Carlisle RC, Bettinger T, Seymour LW (2001) Melittin enables efficient vesicular escape and enhanced nuclear access of nonviral gene delivery vectors. J Biol Chem 276:47550–47555

    PubMed  CAS  Google Scholar 

  • Ohman A, Davydov R, Backlund BM, Langel U, Graslund A (1996) A study of melittin, motilin and galanin in reversed micellar environments, using circular dichroism spectroscopy. Biophys Chem 59:185–192

    PubMed  CAS  Google Scholar 

  • Ohtani Y, Irie T, Fukunaga K, Pitha J (1989) Differential effects of alpha-, beta- and gamma-cyclodextrins on human erythrocytes. Eur J Biochem 186:17–22

    PubMed  CAS  Google Scholar 

  • Okada T, Fujiyoshi Y, Silow M, Navarro J, Landau EM, Shichida Y (2002) Functional role of internal water molecules in rhodopsin revealed by X-ray crystallography. Proc Natl Acad Sci USA 99:5982–5987

    PubMed  CAS  Google Scholar 

  • Oren Z, Shai Y (1997) Selective lysis of bacteria but not mammalian cells by diastereomers of melittin: structure–function study. Biochemistry 36:1826–1835

    PubMed  CAS  Google Scholar 

  • Otoda K, Kimura S, Imanishi Y (1992) Interaction of melittin derivatives with lipid bilayer membrane. Role of basic residues at the C-terminal and their replacement with lactose. Biochim Biophys Acta 1112:1–6

    PubMed  CAS  Google Scholar 

  • Papo N, Shai Y (2003a) Exploring peptide membrane interaction using surface plasmon resonance: differentiation between pore formation versus membrane disruption by lytic peptides. Biochemistry 42:458–466

    CAS  Google Scholar 

  • Papo N, Shai Y (2003b) New lytic peptides based on the d,l-amphipathic helix motif preferentially kill tumor cells compared to normal cells. Biochemistry 42:9346–9354

    CAS  Google Scholar 

  • Parente RA, Nir S, Szoka F (1990) Mechanism of leakage of phospholipid vesicle contents induced by the peptide GALA. Biochemistry 29:8720–8728

    PubMed  CAS  Google Scholar 

  • Pawlak M, Stankowski S, Schwarz G (1991) Melittin induced voltage-dependent conductance in DOPC lipid bilayers. Biochim Biophys Acta 1062:94–102

    PubMed  CAS  Google Scholar 

  • Pérez-Payá E, Houghten RA, Blondelle SE (1995) The role of amphipathicity in the folding, self-association and biological activity of multiple subunit small proteins. J Biol Chem 270:1048–1056

    PubMed  Google Scholar 

  • Pérez-Payá E, Dufourcq J, Braco L, Abad C (1997) Structural characterization of the natural membrane-bound state of melittin: a fluorescence study of a dansylated analogue. Biochim Biophys Acta 1329:223–236

    PubMed  Google Scholar 

  • Pott T, Dufourc EJ (1995) Action of melittin on the DPPC-cholesterol liquid-ordered phase: a solid state 2H-and 31P-NMR study. Biophys J 68:965–977

    PubMed  CAS  Google Scholar 

  • Pott T, Maillet JC, Abad C, Campos A, Dufourcq J, Dufourc EJ (2001) The lipid charge density at the bilayer surface modulates the effects of melittin on membranes. Chem Phys Lipids 109:209–223

    PubMed  CAS  Google Scholar 

  • Pucadyil TJ, Chattopadhyay A (2004) Cholesterol modulates ligand binding and G-protein coupling to serotonin1A receptors from bovine hippocampus. Biochim Biophys Acta 1663:188–200

    PubMed  CAS  Google Scholar 

  • Pucadyil TJ, Chattopadhyay A (2006) Role of cholesterol in the function and organization of G-protein coupled receptors. Prog Lipid Res 45:295–333

    PubMed  CAS  Google Scholar 

  • Qiu W, Zhang L, Kao YT, Lu W, Li T, Kim J, Sollenberger GM, Wang L, Zhong D (2005) Ultrafast hydration dynamics in melittin folding and aggregation: helix formation and tetramer self-assembly. J Phys Chem B 109:16901–16910

    PubMed  CAS  Google Scholar 

  • Quay SC, Condie CC (1983) Conformational studies of aqueous melittin: thermodynamic parameters of the monomer-tetramer self-association reaction. Biochemistry 22:695–700

    PubMed  CAS  Google Scholar 

  • Rabenstein M, Shin YK (1995) A peptide from the heptad repeat of human immunodeficiency virus gp41 shows both membrane binding and coiled-coil formation. Biochemistry 34:13390–13397

    PubMed  CAS  Google Scholar 

  • Raghuraman H, Chattopadhyay A (2003) Organization and dynamics of melittin in environments of graded hydration: a fluorescence approach. Langmuir 19:10332–10341

    CAS  Google Scholar 

  • Raghuraman H, Chattopadhyay A (2004a) Effect of micellar charge on the conformation and dynamics of melittin. Eur Biophys J 33:611–622

    CAS  Google Scholar 

  • Raghuraman H, Chattopadhyay A (2004b) Influence of lipid chain unsaturation on membrane-bound melittin: a fluorescence approach. Biochim Biophys Acta 1665:29–39

    CAS  Google Scholar 

  • Raghuraman H, Chattopadhyay A (2004c) Interaction of melittin with membrane cholesterol: a fluorescence approach. Biophys J 87:2419–2432

    CAS  Google Scholar 

  • Raghuraman H, Chattopadhyay A (2005) Cholesterol inhibits the lytic activity of melittin in erythrocytes. Chem Phys Lipids 134:183–189

    PubMed  CAS  Google Scholar 

  • Raghuraman H, Chattopadhyay A (2006a) Effect of ionic strength on folding and aggregation of the hemolytic peptide melittin in solution. Biopolymers 83:111–121

    CAS  Google Scholar 

  • Raghuraman H, Chattopadhyay A (2006b) Orientation and dynamics of melittin in membranes of varying composition utilizing NBD fluorescence. Biophys J (in press).

  • Raghuraman H, Ganguly S, Chattopadhyay A (2006) Effect of ionic strength on the organization and dynamics of membrane-bound melittin. Biophys Chem 124:115–124

    PubMed  CAS  Google Scholar 

  • Raghuraman H, Kelkar DA, Chattopadhyay A (2005) Novel insights into protein structure and dynamics utilizing the red edge excitation shift approach. In: Geddes CD, Lakowicz JR (eds) Reviews in fluorescence, Vol. 2. Springer, New York, pp 199–222

  • Ramalingam K, Aimoto S, Bello J (1992) Conformational studies of anionic melittin analogues: effect of peptide concentration, pH, ionic strength, and temperature-models for protein folding and halophilic proteins. Biopolymers 32:981–992

    PubMed  CAS  Google Scholar 

  • Rapaport D, Peled R, Nir S, Shai Y (1996) Reversible surface aggregation in pore formation by pardaxin. Biophys J 70:2502–2512

    PubMed  CAS  Google Scholar 

  • Raynor RL, Zheng B, Kuo JF (1991) Membrane interactions of amphiphilic polypeptides mastoparan, melittin, polymyxin B, and cardiotoxin. Differential inhibition of protein kinase C, Ca2+/calmodulin-dependent protein kinase II and synaptosomal membrane Na,K-ATPase, and Na+ pump and differentiation of HL60 cells. J Biol Chem 266:2753–2758

    PubMed  CAS  Google Scholar 

  • Rex S (1996) Pore formation induced by the peptide melittin in different lipid vesicle membranes. Biophys Chem 58:75–85

    PubMed  CAS  Google Scholar 

  • Rex S (2000) A Pro→Ala substitution in melittin affects self-association, membrane binding and pore-formation kinetics due to changes in structural and electrostatic properties. Biophys Chem 85:209–228

    PubMed  CAS  Google Scholar 

  • Rex S, Schwarz G (1998) Quantitative studies on the melittin-induced leakage mechanism of lipid vesicles. Biochemistry 37:2336–2345

    PubMed  CAS  Google Scholar 

  • Rivett DE, Kirkpatrick A, Hewish DR, Reilly W, Werkmeister JA (1996) Dimerization of truncated melittin analogues results in cytolytic peptides. Biochem J 316:525–529

    PubMed  CAS  Google Scholar 

  • Ross EM, Higashijima T (1994) Regulation of G-protein activation by mastoparans and other cationic peptides. Methods Enzymol 237:26–37

    PubMed  CAS  Google Scholar 

  • Rudenko SV, Patelaros SV (1995) Cation-sensitive pore formation in rehydrated erythrocytes. Biochim Biophys Acta 1235:1–9

    PubMed  Google Scholar 

  • Saberwal G, Nagaraj R (1994) Cell-lytic and antibacterial peptides that act by perturbing the barrier function of membranes: facets of their conformational features, structure–function correlation and membrane-perturbing abilities. Biochim Biophys Acta 1197:109–131

    PubMed  CAS  Google Scholar 

  • Sankararamakrishnan R, Sansom MSP (1995) Water-mediated conformational transitions in nicotinic receptor M2 helix bundles: a molecular dynamics study. FEBS Lett 377:377–382

    PubMed  CAS  Google Scholar 

  • Sansom MSP (1991) The biophysics of peptide models of ion channels. Prog Biophys Mol Biol 55:139–235

    PubMed  CAS  Google Scholar 

  • Schroder E, Lubke K, Lehmann M, Beetz I (1971) Haemolytic activity and action on the surface tension of aqueous solutions of synthetic melittins and their derivatives. Experientia 27:764–765

    PubMed  CAS  Google Scholar 

  • Schroeder F, Jefferson JR, Kier AB, Knittel J, Scallen TJ, Wood WG, Hapala I (1991) Membrane cholesterol dynamics: cholesterol domains and kinetic pools. Proc Soc Exp Biol Med 196:235–252

    PubMed  CAS  Google Scholar 

  • Schulze J, Mischeck U, Wigand S, Galla HJ (1987) Incorporation of highly purified melittin into phosphatidylcholines bilayer vesicles. Biochim Biophys Acta 901:101–111

    PubMed  CAS  Google Scholar 

  • Schwarz G, Arbuzova G (1995) Pore kinetics reflected in the dequenching of a lipid vesicle entrapped fluorescent dye. Biochim Biophys Acta 1239:51–57

    PubMed  Google Scholar 

  • Schwarz G, Beschiaschvili A (1989) Thermodynamic and kinetic studies on the association of melittin with a phospholipid bilayer. Biochim Biophys Acta 979:82–90

    PubMed  CAS  Google Scholar 

  • Schwarz G, Zong RT, Popescu T (1992) Kinetics of melittin induced pore formation in the membrane of lipid vesicles. Biochim Biophys Acta 1110:97–104

    PubMed  CAS  Google Scholar 

  • Schwyzer R (1992) Conformations and orientations of amphiphilic peptides induced by artificial lipid membranes: correlations with biological activity. Chemtracts-Biochem Mol Biol 3:347–379

    CAS  Google Scholar 

  • Sekharam KM, Bradrick TD, Georghiou S (1991) Kinetics of melittin binding to phospholipid small unilamellar vesicles. Biochim Biophys Acta 1063:171–174

    PubMed  CAS  Google Scholar 

  • Shai Y (1995) Molecular recognition between membrane-spanning polypeptides. Trends Biochem Sci 20:460–464

    PubMed  CAS  Google Scholar 

  • Shai Y (2002) Mode of action of membrane active antimicrobial peptides. Biopolymers 66:236–248

    PubMed  CAS  Google Scholar 

  • Sharma SV (1992) Melittin resistance: a counterselection for ras transformation. Oncogene 7:193–201

    PubMed  CAS  Google Scholar 

  • Sharma SV (1993) Melittin-induced hyperactivation of phospholipase A2 activity and calcium influx in ras-transformed cells. Oncogene 8:939–947

    PubMed  CAS  Google Scholar 

  • Sheynis T, Sykora J, Benda A, Kolusheva S, Hof M, Jelinek R (2003) Bilayer localization of membrane-active peptides studied in biomimetic vesicles by visible and fluorescence spectroscopies. Eur Biophys J 270:4478–4487

    CAS  Google Scholar 

  • Shipolini RA, Callewaert GL, Cottrell RC, Doonan S, Vernan CA, Banks BEC (1971) Phospholipase A from bee venom. Eur J Biochem 20:459–468

    PubMed  CAS  Google Scholar 

  • Simons K, Ikonen E (2000) How cells handle cholesterol. Science 290:1721–1726

    PubMed  CAS  Google Scholar 

  • Sitaram N, Nagaraj R (1999) Interaction of antimicrobial peptides with biological and model membranes: structural and charge requirements for activity. Biochim Biophys Acta 1462:29–54

    PubMed  CAS  Google Scholar 

  • Song L, Hobaugh MR, Shustak C, Cheley S, Bayley H, Gouaux JE (1996) Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 274:1859–1866

    PubMed  CAS  Google Scholar 

  • Stankowski S, Schwarz UD, Schwarz G (1991) A combined study of aggregation, membrane affinity and pore activity of natural and modified melittin. Biochim Biophys Acta 1069:77–86

    PubMed  CAS  Google Scholar 

  • Steck TL, Ye J, Lange Y (2002) Probing red cell membrane cholesterol movement with cyclodextrin. Biophys J 83:2118–2125

    PubMed  CAS  Google Scholar 

  • Su M, He C, West CA, Mentzer SJ (2001) Cytolytic peptides induce biphasic permeability changes in mammalian cell membranes. J Immunol Methods 252:63–71

    PubMed  CAS  Google Scholar 

  • Subbalakshmi C, Nagaraj R, Sitaram N (1999) Biological activities of C-terminal 15-residue synthetic fragment of melittin: design of an analog with improved antibacterial activity. FEBS Lett 448:62–66

    PubMed  CAS  Google Scholar 

  • Subbarao NK, MacDonald RC (1994) Lipid unsaturation influences melittin-induced leakage of vesicles. Biochim Biophys Acta 1189:101–107

    PubMed  CAS  Google Scholar 

  • Svenaga M, Lee S, Park NG, Aoyagi H, Kato T, Umeda A, Amako K (1989) Basic amphipathic helical peptides induce destabilization and fusion of acidic and neutral liposomes. Biochim Biophys Acta 981:143–150

    Google Scholar 

  • Takei J, Remenyi A, Dempsey CE (1999) Generalised bilayer perturbation from peptide helix dimerisation at membrane surfaces: vesicle lysis induced by disulphide-dimerised melittin analogues. FEBS Lett 442:11–14

    PubMed  CAS  Google Scholar 

  • Talbot JC, Dufourcq J, de Bony J, Faucon JF, Lussan C (1979) Conformational change and self association of monomeric melittin. FEBS Lett 102:191–193

    PubMed  CAS  Google Scholar 

  • Talbot JC, Faucon JF, Dufourcq J (1987) Different states of self-association of melittin in phospholipid bilayers. A resonance energy transfer approach. Eur Biophys J 15:147–157

    PubMed  CAS  Google Scholar 

  • Tanaka H, Matsunaga K, Kawazura H (1992) 23Na and 1H NMR studies on melittin channels activated by tricyclic tranquilizers. Biophys J 63:569–572

    PubMed  CAS  Google Scholar 

  • Teng Q, Scarlata S (1993) Effect of high pressure on the association of melittin to membranes. J Biol Chem 268:12434–12442

    PubMed  CAS  Google Scholar 

  • Terwilliger TC, Eisenberg D (1982a) The structure of melittin. I. Structure determination and partial refinement. J Biol Chem 257:6010–6015

    CAS  Google Scholar 

  • Terwilliger TC, Eisenberg D (1982b) The structure of melittin. II. Interpretation of the structure. J Biol Chem 257:6016–6022

    CAS  Google Scholar 

  • Terwilliger TC, Weissman L, Eisenberg D (1982) The structure of melittin in the form I crystals and its implication for melittin’s lytic and surface activities. Biophys J 37:353–361

    PubMed  CAS  Google Scholar 

  • Toraya S, Nishimura K, Naito A (2004). Dynamic structure of vesicle-bound melittin in a variety of lipid chain lengths by solid-state NMR. Biophys J 87:3323–3335

    PubMed  CAS  Google Scholar 

  • Tosteson MT, Alvarez O, Tosteson DC (1985a) Melittin is able to form anion-seletive channels in lipid bilayers. Regul Pept 13:39–45

    Google Scholar 

  • Tosteson MT, Holmes SJ, Razin M, Tosteson DC (1985b) Melittin lysis of red cells. J Membr Biol 87:35–44

    CAS  Google Scholar 

  • Tosteson MT, Alvarez O, Hubbell W, Bieganski RM, Altenbach C, Caporale LH, Levy JJ, Nutt RF, Rosenblatt M, Tosteson DC (1990) Primary structure of peptides and ion channels. Role of amino acid side chains in voltage gating of melittin channels. Biophys J 58:1367–1375

    PubMed  CAS  Google Scholar 

  • Tosteson MT, Tosteson DC (1981) The sting. Melittin forms channels in lipid bilayers. Biophys J 36:109–116

    PubMed  CAS  Google Scholar 

  • Tosteson MT, Levy JL, Caporale LH, Rosenblatt M, Tosteson DC (1987) Solid-phase synthesis of melittin: purification and functional characterization. Biochemistry 26:6627–6631

    PubMed  CAS  Google Scholar 

  • Unger T, Oren Z, Shai Y (2001) The effect of cyclization of magainin 2 and melittin analogues on structure, function, and model membrane interactions: implication to their mode of action. Biochemistry 40:6388–6397

    PubMed  CAS  Google Scholar 

  • van Veen M, Georgiou GN, Drake AF, Cherry RJ (1995) Circular-dichroism and fluorescene studies of melittin: effects of C-terminal modifications on tetramer formation and binding to phospholipid vesicles. Biochem J 305:785–790

    PubMed  Google Scholar 

  • Vernon LP, Bell JD (1992) Membrane structure, toxins and phospholipase A2 activity. Pharmacol Ther 54:269–295

    PubMed  CAS  Google Scholar 

  • Vogel H (1981) Incorporation of melittin into phosphatidylcholines bilayers. Study of binding and conformational changes. FEBS Lett 134:37–42

    PubMed  CAS  Google Scholar 

  • Vogel H (1987) Comparison of the conformation and orientation of alamethicin and melittin in lipid membranes. Biochemistry 26:4562–4572

    PubMed  CAS  Google Scholar 

  • Vogel H, Jähnig F (1986) The structure of melittin in membranes. Biophys J 50:573–582

    PubMed  CAS  Google Scholar 

  • Voss J, Birmachu W, Hussey DM, Thomas DD (1991) Effects of melittin on molecular dynamics and Ca-ATPase activity in sarcoplasmic reticulum membranes: time-resolved optical anisotropy. Biochemistry 30:7498–7506

    PubMed  CAS  Google Scholar 

  • Wachinger M, Kleinschmidt A, Winder D, von Pechmann N, Ludvigsen A, Neumann M, Holle R, Salmons B, Erfle V, Brack-Werner R (1998) Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression. J Gen Virol 79:731–740

    PubMed  CAS  Google Scholar 

  • Wachinger M, Saermark T, Erfle V (1992) Influence of amphipathic peptides on the HIV-1 production in persistently infected T lymphoma cells. FEBS Lett 309:235–241

    PubMed  CAS  Google Scholar 

  • Wall J, Golding CA, Van Veen M, O’Shea P (1995) The use of fluoresceinphosphatidylethanolamine (FPE) as a real-time probe for peptide–membrane interactions. Mol Membr Biol 12:183–192

    PubMed  CAS  Google Scholar 

  • Watala C, Gwozdzinski K (1992) Melittin-induced alterations in dynamic properties of human red blood cell membranes. Chem Biol Interact 82:135–149

    PubMed  CAS  Google Scholar 

  • Weaver AJ, Kemple MD, Prendergast FG (1989) Characterization of selectively 13C-labeled synthetic melittin and melittin analogues in isotropic solvents by circular dichroism, fluorescence, and NMR spectroscopy. Biochemistry 28:8614–8623

    PubMed  CAS  Google Scholar 

  • Weaver AJ, Kemple MD, Brauner JW, Mendelsohn R, Prendergast FG (1992) Fluorescence, CD, attenuated total reflectance (ATR) FTIR, and carbon-13 NMR characterization of the structure and dynamics of synthetic melittin and melittin analogues in lipid environments. Biochemistry 31:1301–1313

    PubMed  CAS  Google Scholar 

  • Werkmeister JA, Hewish DR, Kirkpatrick A, Rivett DE (2002) Sequence requirements for the activity of membrane-active peptides. J Pept Res 60:232–238

    PubMed  CAS  Google Scholar 

  • Werkmeister JA, Kirkpatrick A, McKenzie JA, Rivett DE (1993) The effect of sequence variations and structure on the cytolytic activity of melittin peptides. Biochim Biophys Acta 1157:50–54

    PubMed  CAS  Google Scholar 

  • White SH, Wimley WC (1998) Hydrophobic interactions of peptides with membrane interfaces. Biochim Biophys Acta 1376:339–352

    PubMed  CAS  Google Scholar 

  • Wilcox W, Eisenberg D (1992) Thermodynamics of melittin tetramerization determined by circular dichroism and implications for protein folding. Protein Sci 1:641–653

    PubMed  CAS  Google Scholar 

  • Wimley WC, White SH (1996) Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat Struct Biol 3:842–848

    PubMed  CAS  Google Scholar 

  • Wimley WC, White SH (2000) Determining the membrane topology of peptides by fluorescence quenching. Biochemistry 39:161–170

    PubMed  CAS  Google Scholar 

  • Wimley WC, Selsted ME, White SH (1994) Interactions between human defensins and lipid bilayers: evidence for formation of multimeric pores. Protein Sci 3:1362–1373

    Article  PubMed  CAS  Google Scholar 

  • Winder D, Gunzburg WH, Erfle V, Salmons B (1998) Expression of antimicrobial peptides has an antitumour effect in human cells. Biochem Biophys Res Commun 242:608–612

    PubMed  CAS  Google Scholar 

  • Wolfe C, Cladera J, O’Shea P (1998) Amino acid sequences which promote and prevent the binding and membrane insertion of surface-active peptides: comparison of melittin and promelittin. Mol Membr Biol 15:221–227

    Article  PubMed  CAS  Google Scholar 

  • Yan H, Li S, Sun X, Mi H, He B (2003) Individual substitution analogs of Mel(12–26), melittin’s C-terminal 15-residue peptide: their antimicrobial and hemolytic actions. FEBS Lett 554:100–104

    PubMed  CAS  Google Scholar 

  • Yang L, Harroun TA, Weiss TA, Ding L, Huang HW (2001) Barrel-stave model or toroidal model? A case study on melittin pores. Biophys J 81:1475–1485

    PubMed  Google Scholar 

  • Yeagle PL (1985) Cholesterol and the cell membrane. Biochim Biophys Acta 822:267–287

    PubMed  CAS  Google Scholar 

  • Yianni YP, Fitton JE, Morgan CG (1986) Lytic effects of melittin and δ-haemolysin from Staphylococcus aureus on vesicles of dipalmitoylphosphatidylcholine. Biochim Biophys Acta 856:91–100

    PubMed  CAS  Google Scholar 

  • Yuan P, Fisher PJ, Prendergast FG, Kemple MD (1996) Structure and dynamics of melittin in lysomyristoyl phosphatidylcholine micelles determined by nuclear magnetic resonance. Biophys J 70:2223–2238

    PubMed  CAS  Google Scholar 

  • Zhao H, Kinnunen PKJ (2002) Binding of the antimicrobial peptide temporin L to liposomes assessed by Trp fluorescence. J Biol Chem 277:25170–25177

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Work in A.C.’s laboratory was supported by the Council of Scientific and Industrial Research, and Department of Science and Technology, Government of India. H.R. thanks the Council of Scientific and Industrial Research for the award of Research Associateship. Some of the work described in this review article was carried out by former and present members of A.C.’s group whose contribution is gratefully acknowledged. We thank members of our laboratory for critically reading the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amitabha Chattopadhyay.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Raghuraman, H., Chattopadhyay, A. Melittin: a Membrane-active Peptide with Diverse Functions. Biosci Rep 27, 189–223 (2007). https://doi.org/10.1007/s10540-006-9030-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10540-006-9030-z

Keywords

Navigation