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.
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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
Allende D, Vidal A, Simon SA, McIntosh TJ (2003) Bilayer interfacial properties modulate the binding of amphipathic peptides. Chem Phys Lipids 122:65–76
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
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
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
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
Bachar M, Becker OM (2000) Protein-induced membrane disorder: a molecular dynamics study of melittin in a dipalmitoylphosphatidylcholine bilayer. Biophys J 78:1359–1375
Baker KJ, East JM, Lee AG (1995) Mechanism of inhibition of the Ca2+-ATPase by melittin. Biochemistry 34:3596–3604
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
Banks BEC, Dempsey CE, Pearce FL, Vernon CA, Wholley TE (1981) New methods of isolating been venom peptides. Anal Biochem 116:48–52
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
Batenburg AM, Hibbeln JC, de Kruijff B (1987) Lipid specific penetration of melittin into phospholipid model membranes. Biochim Biophys Acta 903:155–165
Batenburg AM, van Esch JH, de Kruijff B (1988) Melittin-induced changes of the macroscopic structure of phosphatidylethanolamines. Biochemistry 27:2324–2331
Baumann G, Mueller P (1974) A molecular model of membrane excitability. J Supramol Struct 2:538–557
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
Bechinger B (1997) Structure and functions of channel-forming peptides: magainins, cecropins, melittin and alamethicin. J Membr Biol 156:197–211
Bechinger B (1999) The structure, dynamics and orientation of antimicrobial peptides in membranes by solid-state NMR spectroscopy. Biochim Biophys Acta 1462:157–183
Bechinger B (2004) Structure and function of membrane-lytic peptides. Crit Rev Plant Sci 23:271–292
Bello J, Bello HR, Granados E (1982) Conformation and aggregation of melittin: dependence of pH and concentration. Biochemistry 21:461–465
Benachir T, Lafleur M (1995) Study of vesicle leakage induced by melittin. Biochim Biophys Acta 1235:452–460
Benachir T, Lafleur M (1996) Osmotic and pH transmembrane gradients control the lytic power of melittin. Biophys J 70:831–840
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
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
Bernèche S, Nina M, Roux B (1998) Molecular dynamics simulation of melittin in a dimyristoylphosphatidylcholine bilayer membrane. Biophys J 75:1603–1618
Bernheimer AW, Ruby B (1986) Interactions between membranes and cytolytic peptides. Biochim Biophys Acta 864:123–141
Beschiaschvili G, Baeuerle HD (1991) Effective charge of melittin upon interaction with POPC vesicles. Biochim Biophys Acta 1068:195–200
Beschiaschvili G, Seelig J (1990) Melittin binding to mixed phosphatidylglycerol/phosphatidylcholine membranes. Biochemistry 29:52–58
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
Bismuto E, Sirangelo I, Irace G (1993) Folding and dynamics of melittin in reversed micelles. Biochim Biophys Acta 1146:213–218
Blondelle SE, Houghten RA (1991a) Hemolytic and antimicrobial activities of twenty-four individual omission analogues of melittin. Biochemistry 30:4671–4678
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
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
Bos JL (1989) ras oncogenes in human cancer: a review. Cancer Res 49:4682–4689
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
Bradrick TD, Georghiou S (1987) Kinetics of melittin-induced fusion of dipalmitoylphosphatidylcholine small unilamellar vesicles. Biochim Biophys Acta 905:494–498
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
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
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
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
Brown LR, Wüthrich K (1981) Melittin bound to dodecylphosphocholine micelles. H-NMR assignments and global conformational features. Biochim Biophys Acta 647:95–111
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
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
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
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
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
Chattopadhyay A (2003) Exploring membrane organization and dynamics by the wavelength-selective fluorescence approach. Chem Phys Lipids 122:3–17
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
Chattopadhyay A, Rukmini R (1993) Restricted mobility of the sole tryptophan in membrane-bound melittin. FEBS Lett 335:341–344
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
Christian AE, Haynes MP, Phillips MC, Rothblat GH (1997) Use of cyclodextrins for manipulating cellular cholesterol content. J Lipid Res 38:2264–2272
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
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
Cserhati T, Szogyi M (1994) Interaction of phospholipids with proteins and peptides. New advances IV. Int J Biochem 26:1–18
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
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
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
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
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
Dawson CR, Drake AF, Helliwell J, Hider RC (1978) The interaction of bee melittin with lipid bilayer membranes. Biochim Biophys Acta 510:75–86
de Kruijff B (1990) Cholesterol as a target for toxins. Biosci Rep 10:127–130
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
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
Demchenko AP (1988) Red-edge-excitation fluorescence spectroscopy of single-tryptophan proteins. Eur Biophys J 16:121–129
Demchenko AP (2002) The red-edge effects: 30 years of exploration. Luminescence 17:19–42
Dempsey CE (1988) pH-dependence of hydrogen-exchange from backbone peptide amides of melittin in methanol. Biochemistry 27:6893–6901
Dempsey CE (1990) The actions of melittin on membranes. Biochim Biophys Acta 1031:143–161
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
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
Dempsey CE, Sternberg B (1991) Reversible disc-micellization of dimyristoylphosphatidylcholine bilayers induced by melittin and [Ala-14]melittin. Biochim Biophys Acta 1061:175–184
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
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
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
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
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
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
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
El Jastimi R, Lafleur M (1999) A dual-probe fluorescence method to examine selective perturbations of membrane permeability by melittin. Biospectroscopy 5:133–140
Epand RM, Vogel HJ (1999) Diversity of antimicrobial peptides and their mechanisms of action. Biochim Biophys Acta 1462:11–28
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
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
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
Fletcher JE, Jiang MS (1993) Possible mechanisms of action of cobra snake venom cardiotoxins and bee venom melittin. Toxicon 31:669–695
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
Frey S, Tamm LK (1991) Orientation of melittin in phospholipid bilayers. A polarized attenuated total reflection infrared study. Biophys J 60:922–930
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
Fung LK, Stryer L (1978) Surface density determination in membranes by fluorescence energy transfer. Biochemistry 17:5241–5248
Garnier J, Gaye P, Mercier JC, Robson B (1980) Structural properties of signal peptides and their membrane insertion. Biochimie 62:231–239
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
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
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
Golding C, O’Shea P (1995) The interactions of signal sequences with membranes. Biochem Soc Trans 23:971–976
Gómara MJ, Nir S, Nieva JL (2003) Effects of sphingomyelin on melittin pore formation. Biochim Biophys Acta 1612:83–89
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
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
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
Habermann E (1972) Bee and wasp venoms. Science 177:314–322
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
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
Hermetter A, Lakowicz JR (1986) The aggregation state of mellitin in lipid bilayers. An energy transfer study. J Biol Chem 261:8243–8248
Herwaldt BL (1999) Leishmaniasis. Lancet 354:1191–1199
Hider RC, Khader F, Tatham AS (1983) Lytic activity of monomeric and oligomeric melittin. Biochim Biophys Acta 728:206–214
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
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
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
Ho C, Stubbs CD (1992) Hydration at the membrane protein–lipid interface. Biophys J 63:897–902
Hristova K, Dempsey CE, White SH (2001) Structure, location, and lipid perturbations of melittin at the membrane interface. Biophys J 80:801–811
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
Huang HW (2000) Action of antimicrobial peptides: two-state model. Biochemistry 39:8347–8352
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
Hung WC, Lee MT (2006) The interaction of melittin with E. coli membrane: the role of cardiolipin. Chinese J Phys 44:137–149
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
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
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
John E, Jähnig F (1988) Dynamics of melittin in water and membranes as determined by fluorescence anisotropy decay. Biophys J 54:817–827
John E, Jähnig F (1991) Aggregation state of melittin in lipid vesicle membranes. Biophys J 60:319–328
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
Kaiser ET, Kezdy FJ (1983) Secondary structures of proteins and peptides in amphiphilic environment. Proc Natl Acad Sci USA 80:1137–1143
Kaiser ET, Kezdy FJ (1984) Amphiphilic secondary structure: design of peptide hormones. Science 223:249–255
Kaszycki P, Wasylewski Z (1990) Fluorescence-quenching-resolved spectra of melittin in lipid bilayers. Biochim Biophys Acta 1040:337–345
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
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
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
Knoppel E, Eisenberg D, Wickner W (1979) Interactions of melittin, a preprotein model, with detergents. Biochemistry 18:4177–4181
Kourie JI, Shorthouse AA (2000) Properties of cytotoxic peptide-formed ion channels. Am J Physiol Cell Physiol 278:C1063–C1087
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
Kriech MA, Conboy JC (2003) Label-free chiral detection of melittin binding to a membrane. J Am Chem Soc 125:1148–1149
Kuchinka E, Seelig J (1989) Interaction of melittin with phosphatidylcholine membranes. Binding isotherm and lipid head-group conformation. Biochemistry 28:4216–4221
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
Ladokhin AS, White SH (1999) Folding of amphipathic alpha-helices on membranes: energetics of helix formation by melittin. J Mol Biol 285:1363–1369
Ladokhin AS, White SH (2001) ‘Detergent-like’ permeabilization of anionic lipid vesicles by melittin. Biochim Biophys Acta 1514:253–260
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
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
Lauterwein J, Brown LR, Wüthrich K (1980) High-resolution 1H-NMR studies of monomeric melittin in aqueous solution. Biochim Biophys Acta 622:219–230
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
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
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
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
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
Lin JH, Baumgaertner A (2000) Stability of a melittin pore in a lipid bilayer: a molecular dynamics study. Biophys J 78:1714–1724
Liscum L, Underwood KW (1995) Intracellular cholesterol transport and compartmentation. J Biol Chem 270:15443–15446
Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35:13723–13728
Luisi PL, Magid LJ (1986) Solubilization of enzymes and nucleic acids in hydrocarbon micellar solutions. CRC Crit Rev Biochem 20:409–474
Luisi PL, Giomini M, Pileni MP, Robinson BH (1988) Reverse micelles as hosts for proteins and small molecules. Biochim Biophys Acta 947:209–246
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
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
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
Maloy WL, Kari UP (1995) Structure–activity studies on magainins and other host defense peptides. Biopolymers 37:105–122
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
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
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
Matsuzaki K, Yoneyama S, Miyajima K (1997) Pore formation and translocation of melittin. Biophys J 73:831–838
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
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
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
Mitchell DC Litman BJ (1998) Effect of cholesterol on molecular order and dynamics in highly polyunsaturated phospholipid bilayers. Biophys J 75:896–908
Monette M, Lafleur M (1995) Modulation of melittin-induced lysis by surface charge density of membranes. Biophys J 68:187–195
Monette M, Lafleur M (1996) Influence of lipid chain unsaturation on melittin-induced micellization. Biophys J 70:2195–2202
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
Morgan CG, Williamson H, Fuller S, Hudson B (1983) Melittin induces fusion of unilamellar phospholipid vesicles. Biochim Biophys Acta 732:668–674
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
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
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
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
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
Neumann W, Habermann E, Hansen H (1953) Differentiation of two hemolytic factors in bee venom. Naunyn-Schmiedebergs Arch Exp Path Pharma 217:130–143
Niemz A, Tirrel DA (2001) Self-association and membrane-binding behavior of melittins containing trifluoroleucine. J Am Chem Soc 123:7407–7413
Nir S, Nieva JL (2000) Interactions of peptides with liposomes: pore formation and fusion. Prog Lipid Res 39:181–206
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
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
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
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
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
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
Oren Z, Shai Y (1997) Selective lysis of bacteria but not mammalian cells by diastereomers of melittin: structure–function study. Biochemistry 36:1826–1835
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
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
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
Parente RA, Nir S, Szoka F (1990) Mechanism of leakage of phospholipid vesicle contents induced by the peptide GALA. Biochemistry 29:8720–8728
Pawlak M, Stankowski S, Schwarz G (1991) Melittin induced voltage-dependent conductance in DOPC lipid bilayers. Biochim Biophys Acta 1062:94–102
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
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
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
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
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
Pucadyil TJ, Chattopadhyay A (2006) Role of cholesterol in the function and organization of G-protein coupled receptors. Prog Lipid Res 45:295–333
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
Quay SC, Condie CC (1983) Conformational studies of aqueous melittin: thermodynamic parameters of the monomer-tetramer self-association reaction. Biochemistry 22:695–700
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
Raghuraman H, Chattopadhyay A (2003) Organization and dynamics of melittin in environments of graded hydration: a fluorescence approach. Langmuir 19:10332–10341
Raghuraman H, Chattopadhyay A (2004a) Effect of micellar charge on the conformation and dynamics of melittin. Eur Biophys J 33:611–622
Raghuraman H, Chattopadhyay A (2004b) Influence of lipid chain unsaturation on membrane-bound melittin: a fluorescence approach. Biochim Biophys Acta 1665:29–39
Raghuraman H, Chattopadhyay A (2004c) Interaction of melittin with membrane cholesterol: a fluorescence approach. Biophys J 87:2419–2432
Raghuraman H, Chattopadhyay A (2005) Cholesterol inhibits the lytic activity of melittin in erythrocytes. Chem Phys Lipids 134:183–189
Raghuraman H, Chattopadhyay A (2006a) Effect of ionic strength on folding and aggregation of the hemolytic peptide melittin in solution. Biopolymers 83:111–121
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
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
Rapaport D, Peled R, Nir S, Shai Y (1996) Reversible surface aggregation in pore formation by pardaxin. Biophys J 70:2502–2512
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
Rex S (1996) Pore formation induced by the peptide melittin in different lipid vesicle membranes. Biophys Chem 58:75–85
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
Rex S, Schwarz G (1998) Quantitative studies on the melittin-induced leakage mechanism of lipid vesicles. Biochemistry 37:2336–2345
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
Ross EM, Higashijima T (1994) Regulation of G-protein activation by mastoparans and other cationic peptides. Methods Enzymol 237:26–37
Rudenko SV, Patelaros SV (1995) Cation-sensitive pore formation in rehydrated erythrocytes. Biochim Biophys Acta 1235:1–9
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
Sankararamakrishnan R, Sansom MSP (1995) Water-mediated conformational transitions in nicotinic receptor M2 helix bundles: a molecular dynamics study. FEBS Lett 377:377–382
Sansom MSP (1991) The biophysics of peptide models of ion channels. Prog Biophys Mol Biol 55:139–235
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
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
Schulze J, Mischeck U, Wigand S, Galla HJ (1987) Incorporation of highly purified melittin into phosphatidylcholines bilayer vesicles. Biochim Biophys Acta 901:101–111
Schwarz G, Arbuzova G (1995) Pore kinetics reflected in the dequenching of a lipid vesicle entrapped fluorescent dye. Biochim Biophys Acta 1239:51–57
Schwarz G, Beschiaschvili A (1989) Thermodynamic and kinetic studies on the association of melittin with a phospholipid bilayer. Biochim Biophys Acta 979:82–90
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
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
Sekharam KM, Bradrick TD, Georghiou S (1991) Kinetics of melittin binding to phospholipid small unilamellar vesicles. Biochim Biophys Acta 1063:171–174
Shai Y (1995) Molecular recognition between membrane-spanning polypeptides. Trends Biochem Sci 20:460–464
Shai Y (2002) Mode of action of membrane active antimicrobial peptides. Biopolymers 66:236–248
Sharma SV (1992) Melittin resistance: a counterselection for ras transformation. Oncogene 7:193–201
Sharma SV (1993) Melittin-induced hyperactivation of phospholipase A2 activity and calcium influx in ras-transformed cells. Oncogene 8:939–947
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
Shipolini RA, Callewaert GL, Cottrell RC, Doonan S, Vernan CA, Banks BEC (1971) Phospholipase A from bee venom. Eur J Biochem 20:459–468
Simons K, Ikonen E (2000) How cells handle cholesterol. Science 290:1721–1726
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
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
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
Steck TL, Ye J, Lange Y (2002) Probing red cell membrane cholesterol movement with cyclodextrin. Biophys J 83:2118–2125
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
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
Subbarao NK, MacDonald RC (1994) Lipid unsaturation influences melittin-induced leakage of vesicles. Biochim Biophys Acta 1189:101–107
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
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
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
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
Tanaka H, Matsunaga K, Kawazura H (1992) 23Na and 1H NMR studies on melittin channels activated by tricyclic tranquilizers. Biophys J 63:569–572
Teng Q, Scarlata S (1993) Effect of high pressure on the association of melittin to membranes. J Biol Chem 268:12434–12442
Terwilliger TC, Eisenberg D (1982a) The structure of melittin. I. Structure determination and partial refinement. J Biol Chem 257:6010–6015
Terwilliger TC, Eisenberg D (1982b) The structure of melittin. II. Interpretation of the structure. J Biol Chem 257:6016–6022
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
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
Tosteson MT, Alvarez O, Tosteson DC (1985a) Melittin is able to form anion-seletive channels in lipid bilayers. Regul Pept 13:39–45
Tosteson MT, Holmes SJ, Razin M, Tosteson DC (1985b) Melittin lysis of red cells. J Membr Biol 87:35–44
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
Tosteson MT, Tosteson DC (1981) The sting. Melittin forms channels in lipid bilayers. Biophys J 36:109–116
Tosteson MT, Levy JL, Caporale LH, Rosenblatt M, Tosteson DC (1987) Solid-phase synthesis of melittin: purification and functional characterization. Biochemistry 26:6627–6631
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
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
Vernon LP, Bell JD (1992) Membrane structure, toxins and phospholipase A2 activity. Pharmacol Ther 54:269–295
Vogel H (1981) Incorporation of melittin into phosphatidylcholines bilayers. Study of binding and conformational changes. FEBS Lett 134:37–42
Vogel H (1987) Comparison of the conformation and orientation of alamethicin and melittin in lipid membranes. Biochemistry 26:4562–4572
Vogel H, Jähnig F (1986) The structure of melittin in membranes. Biophys J 50:573–582
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
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
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
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
Watala C, Gwozdzinski K (1992) Melittin-induced alterations in dynamic properties of human red blood cell membranes. Chem Biol Interact 82:135–149
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
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
Werkmeister JA, Hewish DR, Kirkpatrick A, Rivett DE (2002) Sequence requirements for the activity of membrane-active peptides. J Pept Res 60:232–238
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
White SH, Wimley WC (1998) Hydrophobic interactions of peptides with membrane interfaces. Biochim Biophys Acta 1376:339–352
Wilcox W, Eisenberg D (1992) Thermodynamics of melittin tetramerization determined by circular dichroism and implications for protein folding. Protein Sci 1:641–653
Wimley WC, White SH (1996) Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat Struct Biol 3:842–848
Wimley WC, White SH (2000) Determining the membrane topology of peptides by fluorescence quenching. Biochemistry 39:161–170
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
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
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
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
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
Yeagle PL (1985) Cholesterol and the cell membrane. Biochim Biophys Acta 822:267–287
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
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
Zhao H, Kinnunen PKJ (2002) Binding of the antimicrobial peptide temporin L to liposomes assessed by Trp fluorescence. J Biol Chem 277:25170–25177
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.
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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
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DOI: https://doi.org/10.1007/s10540-006-9030-z