Summary: Basic polypeptide from the venom of the honey bee (Apis mellifera). It contains 26 amino acids, has cytolytic properties, causes contracture of muscle, releases histamine, and disrupts surface tension, probably due to lysis of cell and mitochondrial membranes.

Top Publications

  1. Budnik B, Tsybin Y, Håkansson P, Zubarev R. Ionization energies of multiply protonated polypeptides obtained by tandem ionization in Fourier transform mass spectrometers. J Mass Spectrom. 2002;37:1141-4 pubmed
    ..8 + 1.1z. The average IE increase of 1.1 eV/charge is attributed to Coulombic repulsion. The deduced ionization energy of a neutral polypeptide molecule, 9.8 +/- 0.3 eV, is consistent with literature expectations. ..
  2. Gordon Grossman M, Zimmermann H, Wolf S, Shai Y, Goldfarb D. Investigation of model membrane disruption mechanism by melittin using pulse electron paramagnetic resonance spectroscopy and cryogenic transmission electron microscopy. J Phys Chem B. 2012;116:179-88 pubmed publisher
    ..This work further demonstrates the applicability and potential of pulse EPR techniques for the study of peptide-membrane interactions. ..
  3. Pandey B, Ahmad A, Asthana N, Azmi S, Srivastava R, Srivastava S, et al. Cell-selective lysis by novel analogues of melittin against human red blood cells and Escherichia coli. Biochemistry. 2010;49:7920-9 pubmed publisher
  4. Allende D, Simon S, McIntosh T. Melittin-induced bilayer leakage depends on lipid material properties: evidence for toroidal pores. Biophys J. 2005;88:1828-37 pubmed
    ..All of these results demonstrate the importance of bilayer material properties on melittin-induced leakage and indicate that the melittin-induced pores are defects in the bilayer lined in part by lipid molecules. ..
  5. Toraya S, Nagao T, Norisada K, Tuzi S, Saito H, Izumi S, et al. Morphological behavior of lipid bilayers induced by melittin near the phase transition temperature. Biophys J. 2005;89:3214-22 pubmed
    ..On the other hand, additional large amplitude motion induced by melittin at a temperature near the Tc breaks down the magnetic alignment. ..
  6. Rapson A, Hossain M, Wade J, Nice E, Smith T, Clayton A, et al. Structural dynamics of a lytic peptide interacting with a supported lipid bilayer. Biophys J. 2011;100:1353-61 pubmed publisher
    ..The data indicate a highly ordered and polar environment near the center of the melittin helix consistent with the formation of a toroidal pore. ..
  7. Ningsih Z, Hossain M, Wade J, Clayton A, Gee M. Slow insertion kinetics during interaction of a model antimicrobial peptide with unilamellar phospholipid vesicles. Langmuir. 2012;28:2217-24 pubmed publisher
    ..Analysis of the complex kinetics revealed several intermediates. We assign these to distinct states of the peptide formed during helix insertion into the vesicle membrane that are intermediate to lytic pore formation. ..
  8. Kokot G, Mally M, Svetina S. The dynamics of melittin-induced membrane permeability. Eur Biophys J. 2012;41:461-74 pubmed publisher
    ..The relatively stable "average MLT pore" characteristics can be deduced from the proposed model. ..
  9. Raghuraman H, Chattopadhyay A. Effect of ionic strength on folding and aggregation of the hemolytic peptide melittin in solution. Biopolymers. 2006;83:111-21 pubmed
    ..Taken together, these results constitute the first report showing that REES could be used as a sensitive tool to monitor the aggregation behavior of melittin in particular and other proteins and peptides in general. ..

More Information


  1. Miura Y. NMR studies on the monomer-tetramer transition of melittin in an aqueous solution at high and low temperatures. Eur Biophys J. 2012;41:629-36 pubmed publisher
    ..The tetramer has maximum conformation stability at around 20 °C, and cooperativity of the heat-denaturation is extremely low. ..
  2. Abrunhosa F, Faria S, Gomes P, Tomaz I, Pessoa J, Andreu D, et al. Interaction and lipid-induced conformation of two cecropin-melittin hybrid peptides depend on peptide and membrane composition. J Phys Chem B. 2005;109:17311-9 pubmed
    ..Moreover, delicate modulations in behavior were observed depending on the peptide. ..
  3. Mally M, Majhenc J, Svetina S, Zeks B. The response of giant phospholipid vesicles to pore-forming peptide melittin. Biochim Biophys Acta. 2007;1768:1179-89 pubmed
  4. Schlamadinger D, Gable J, Kim J. Hydrogen bonding and solvent polarity markers in the uv resonance raman spectrum of tryptophan: application to membrane proteins. J Phys Chem B. 2009;113:14769-78 pubmed publisher
  5. Sengupta D, Leontiadou H, Mark A, Marrink S. Toroidal pores formed by antimicrobial peptides show significant disorder. Biochim Biophys Acta. 2008;1778:2308-17 pubmed publisher
    ..It was also found that in the absence of counter ions pores not only form more rapidly but lead to membrane rupture. The rupture process occurs via a novel recursive poration pathway, which we coin the Droste mechanism. ..
  6. Klocek G, Seelig J. Melittin interaction with sulfated cell surface sugars. Biochemistry. 2008;47:2841-9 pubmed publisher
    ..Nisin Z shows activity against various Gram-positive bacteria. Isothermal titration calorimetry demonstrates that magainin 2 and nisin Z do not bind to HS (5-50 degrees C, 10 mM Tris, and 100 mM NaCl at pH 7.4). ..
  7. Popplewell J, Swann M, Freeman N, McDonnell C, Ford R. Quantifying the effects of melittin on liposomes. Biochim Biophys Acta. 2007;1768:13-20 pubmed
  8. Raghuraman H, Chattopadhyay A. Melittin: a membrane-active peptide with diverse functions. Biosci Rep. 2007;27:189-223 pubmed
    ..The recent applications of melittin in various cellular processes are discussed. ..
  9. Mihajlovic M, Lazaridis T. Antimicrobial peptides in toroidal and cylindrical pores. Biochim Biophys Acta. 2010;1798:1485-93 pubmed publisher
    ..The melittin tetramer interacts more strongly with lipids in the toroidal pore than in the cylindrical one, due to more favorable electrostatic interactions. ..
  10. Strömstedt A, Wessman P, Ringstad L, Edwards K, Malmsten M. Effect of lipid headgroup composition on the interaction between melittin and lipid bilayers. J Colloid Interface Sci. 2007;311:59-69 pubmed
  11. Son D, Lee J, Lee Y, Song H, Lee C, Hong J. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Ther. 2007;115:246-70 pubmed
    ..The conjugation of cell lytic peptide (melittin) with hormone receptors and gene therapy carrying melittin can be useful as a novel targeted therapy for some types of cancer, such as prostate and breast cancer. ..
  12. Yu Y, Vroman J, Bae S, Granick S. Vesicle budding induced by a pore-forming peptide. J Am Chem Soc. 2010;132:195-201 pubmed publisher
    ..Line tension is experimentally shown to be essential for budding in this multicomponent membrane. ..
  13. Park S, Kim J, Shin S, Jeong C, Kim M, Shin S, et al. Investigation of toroidal pore and oligomerization by melittin using transmission electron microscopy. Biochem Biophys Res Commun. 2006;343:222-8 pubmed
    ..The toroidal pores composed of 7-8 nm diameter rings that encircled 3.5-4.5 nm diameter cavities on zwitterionic lipid vesicles. ..
  14. Lee M, Hung W, Chen F, Huang H. Mechanism and kinetics of pore formation in membranes by water-soluble amphipathic peptides. Proc Natl Acad Sci U S A. 2008;105:5087-92 pubmed publisher
    ..The mechanism includes a negative feedback that makes peptide-induced pores stable with a well defined size, contrary to the suggestion that peptides disintegrate the membrane in a detergent-like manner. ..
  15. Toraya S, Nishimura K, Naito A. Dynamic structure of vesicle-bound melittin in a variety of lipid chain lengths by solid-state NMR. Biophys J. 2004;87:3323-35 pubmed
    ..These analyses further lead to the conclusion that the alpha-helices of melittin molecules penetrate the hydrophobic cores of the bilayers incompletely as a pseudo-trans-membrane structure and induce fusion and disruption of vesicles. ..
  16. Ladokhin A, White S. Folding of amphipathic alpha-helices on membranes: energetics of helix formation by melittin. J Mol Biol. 1999;285:1363-9 pubmed
    ..These two values provide a useful rule of thumb for estimating the energetic consequences of membrane-induced secondary structure formation. ..
  17. Maget Dana R. The monolayer technique: a potent tool for studying the interfacial properties of antimicrobial and membrane-lytic peptides and their interactions with lipid membranes. Biochim Biophys Acta. 1999;1462:109-40 pubmed
    ..The penetration of these antimicrobial peptides into phospholipid monolayer model membranes, as well as their interactions with lipids in mixed films, are also emphasized. ..
  18. Ladokhin A, White S. 'Detergent-like' permeabilization of anionic lipid vesicles by melittin. Biochim Biophys Acta. 2001;1514:253-60 pubmed
    ..The apparent inhibition of MLT permeabilization by anionic membranes may thus be due to suppression of translocation ability. ..
  19. Mancheño J, Onaderra M, Martinez del Pozo A, Díaz Achirica P, Andreu D, Rivas L, et al. Release of lipid vesicle contents by an antibacterial cecropin A-melittin hybrid peptide. Biochemistry. 1996;35:9892-9 pubmed
    ..This suggests that acidic phospholipids may modulate the effect of the peptide on membranes. ..
  20. Bechinger B. Structure and functions of channel-forming peptides: magainins, cecropins, melittin and alamethicin. J Membr Biol. 1997;156:197-211 pubmed
  21. Matsuzaki K, Yoneyama S, Miyajima K. Pore formation and translocation of melittin. Biophys J. 1997;73:831-8 pubmed
    ..A novel model for the melittin pore formation was discussed in comparison with other pore-forming peptides. ..
  22. Dempsey C. The actions of melittin on membranes. Biochim Biophys Acta. 1990;1031:143-61 pubmed
  23. Lazarev V, Parfenova T, Gularyan S, Misyurina O, Akopian T, Govorun V. Induced expression of melittin, an antimicrobial peptide, inhibits infection by Chlamydia trachomatis and Mycoplasma hominis in a HeLa cell line. Int J Antimicrob Agents. 2002;19:133-7 pubmed
    ..We showed inhibition of C. trachomatis and M. hominis infection after the introduction of recombinant plasmid vectors expressing the melittin gene into the infected cell culture...
  24. Higashino Y, Matsui A, Ohki K. Membrane fusion between liposomes composed of acidic phospholipids and neutral phospholipids induced by melittin: a differential scanning calorimetric study. J Biochem. 2001;130:393-7 pubmed
    ..These results indicate that a peptide including hydrophobic and basic regions can mediate membrane fusion between neutral and acidic liposomes by hydrophobic and electrostatic interactions. ..
  25. Yang L, Harroun T, Weiss T, Ding L, Huang H. Barrel-stave model or toroidal model? A case study on melittin pores. Biophys J. 2001;81:1475-85 pubmed
  26. Naito A, Nagao T, Norisada K, Mizuno T, Tuzi S, Saito H. Conformation and dynamics of melittin bound to magnetically oriented lipid bilayers by solid-state (31)P and (13)C NMR spectroscopy. Biophys J. 2000;78:2405-17 pubmed
    ..Pore formation was clearly observed below the T(m) in the initial stage of lysis by microscope. This is considered to be caused by the association of melittin molecules in the lipid bilayer. ..
  27. Roccatano D, Fioroni M, Zacharias M, Colombo G. Effect of hexafluoroisopropanol alcohol on the structure of melittin: a molecular dynamics simulation study. Protein Sci. 2005;14:2582-9 pubmed
    ..Finally, a stabilizing effect promoted by the presence of counter-ions was also observed in the simulations. ..
  28. Yalcin M, Savci V. Cardiovascular effects of centrally injected melittin in hemorrhaged hypotensive rats: the investigation of peripheral mechanisms. Neuropeptides. 2007;41:465-75 pubmed
    ..The increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity mediate the pressor responses to melittin in normal and hypotensive conditions. ..
  29. Jeong N, Kim J, Park S, Lee J, Gopal R, Yoo S, et al. Antibiotic and synergistic effect of Leu-Lys rich peptide against antibiotic resistant microorganisms isolated from patients with cholelithiasis. Biochem Biophys Res Commun. 2010;399:581-6 pubmed publisher
    ..aeruginosa. Therefore, these peptides may be used as a lead drug for the treatment of acquired pathogens from patients with cholelithiasis who are affected with antibiotic-resistant bacteria...
  30. Bucki R, Pastore J, Randhawa P, Vegners R, Weiner D, Janmey P. Antibacterial activities of rhodamine B-conjugated gelsolin-derived peptides compared to those of the antimicrobial peptides cathelicidin LL37, magainin II, and melittin. Antimicrob Agents Chemother. 2004;48:1526-33 pubmed
  31. Gerig J. Structure and solvation of melittin in hexafluoroacetone/water. Biopolymers. 2004;74:240-7 pubmed
    ..These results indicate that interactions of both HFA and water are qualitatively different from those present when the peptide is dissolved in 35% hexafluoro-2-propanol/water, a chemically similar helix-supporting solvent system. ..
  32. Karasawa T, Sugawara M. A surface plasmon resonance sensor for substance P using gold-modified calmodulin and melittin. Anal Sci. 2005;21:1431-6 pubmed
    ..The potential use of the present sensor for the quantification of SP in mouse brain extracts is demonstrated. ..
  33. Magzoub M, Oglecka K, Pramanik A, Göran Eriksson L, Gräslund A. Membrane perturbation effects of peptides derived from the N-termini of unprocessed prion proteins. Biochim Biophys Acta. 2005;1716:126-36 pubmed
    ..The membrane perturbation effects of the N-terminal prion peptides suggest that they form transient pores (similar to melittin) causing toxicity in parallel with their cellular trafficking. ..
  34. Sosa L, Alfaro E, Santiago J, Narváez D, Rosado M, Rodríguez A, et al. The structure, molecular dynamics, and energetics of centrin-melittin complex. Proteins. 2011;79:3132-43 pubmed publisher
  35. Mallik P, Shi H, Pande J. RNA aptamers targeted for human ?A-crystallin do not bind ?B-crystallin, and spare the ?-crystallin domain. Biochem Biophys Res Commun. 2017;491:423-428 pubmed publisher
  36. Maher S, McClean S. Melittin exhibits necrotic cytotoxicity in gastrointestinal cells which is attenuated by cholesterol. Biochem Pharmacol. 2008;75:1104-14 pubmed
    ..Overall, although melittin appears to stimulate necrosis, with careful dosage selection the peptide could be considered for the oral delivery of poorly bioavailable drugs. ..
  37. Hickel A, Danner Pongratz S, Amenitsch H, Degovics G, Rappolt M, Lohner K, et al. Influence of antimicrobial peptides on the formation of nonlamellar lipid mesophases. Biochim Biophys Acta. 2008;1778:2325-33 pubmed publisher
    ..Both mechanisms prevent transmembrane contact required to form either an inverted hexagonal phase or fusion pores, as precursors of the cubic phase. ..
  38. Zhao Y, Feng J, Wang Z, Liang A, Yang B. Characterization of melittin binding to Euplotes octocarinatus centrin. Spectrochim Acta A Mol Biomol Spectrosc. 2008;70:884-7 pubmed
    ..Based on the fluorescence titration curves, the 1:1 stoichiometric ratio of holoEoCen to ME was confirmed. In addition, the conditional binding constant of holoEoCen with ME was calculated to be logKME-holoEoCen=6.59+/-0.14. ..
  39. Dixon R, Muddiman D. Quantitative comparison of a flared and a standard heated metal capillary inlet with a voltage-assisted air amplifier on an electrospray ionization linear ion trap mass spectrometer. Rapid Commun Mass Spectrom. 2007;21:3207-12 pubmed
    ..The compatibility of a voltage-assisted air amplifier is explored for both types of capillaries and in all cases resulted in improved ion abundance and spray current. ..
  40. Yu M, Wang Y, Li X, Fang S, Xue J, Song J. [Synthesis of peptide fragment of melittin and the function of rheumatoid arthritis cure]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2005;22:1031-5 pubmed
    ..The hydrophile peptide fragment of melittin may retain anti-rheumatoid arthritis activity and reduce the melittin-induced hemolysis and hypersusceptibility. ..
  41. Gerig J. Structure and solvation of melittin in 1,1,1,3,3,3-hexafluoro-2-propanol/water. Biophys J. 2004;86:3166-75 pubmed
    ..For the remainder of the molecule, solute-solvent NOEs are consistent with preferential solvation of the peptide by the fluoroalcohol component of the solvent mixture. ..
  42. Mihajlovic M, Lazaridis T. Antimicrobial peptides bind more strongly to membrane pores. Biochim Biophys Acta. 2010;1798:1494-502 pubmed publisher
    ..An initial test on a melittin-based mutant seems to support this hypothesis. ..
  43. Lee V, Tu W, Jinn T, Peng C, Lin L, Tzen J. Molecular cloning of the precursor polypeptide of mastoparan B and its putative processing enzyme, dipeptidyl peptidase IV, from the black-bellied hornet, Vespa basalis. Insect Mol Biol. 2007;16:231-7 pubmed
    ..Subsequently, a putative dipeptidyl peptidase IV cDNA fragment was cloned from Vespa basalis venom gland. The prosequence may possibly be removed via sequential liberation of dipeptides during the processing of mastoparan B. ..
  44. Williams D, Hawkridge A, Muddiman D. Sub parts-per-million mass measurement accuracy of intact proteins and product ions achieved using a dual electrospray ionization quadrupole fourier transform ion cyclotron resonance mass spectrometer. J Am Soc Mass Spectrom. 2007;18:1-7 pubmed
    ..0 ppm to 1.1 ppm, with an average of -0.9 ppm. This method requires limited modification to ESI-FT-ICR mass spectrometers and is applicable for both positive and negative ionization modes. ..
  45. Iwashita N, Nosaka S, Koyama N. Involvement of peripheral NMDA receptor in melittin-induced thermographic flare. Neurochem Res. 2012;37:2222-8 pubmed publisher
    ..We suggest that topical administration of NMDA receptor antagonists could be an effective treatment of neuro-inflammatory pain. ..
  46. Khajehpour M, Troxler T, Nanda V, Vanderkooi J. Melittin as model system for probing interactions between proteins and cyclodextrins. Proteins. 2004;55:275-87 pubmed
    ..HPBCD inhibits the aggregation of melittin. This inhibition and the spectroscopic results are consistent with the lone aromatic tryptophan of the peptide being intercalated within HPBCD. ..
  47. Doltchinkova V, Georgieva K, Traytcheva N, Slavov C, Mishev K. Melittin-induced changes in thylakoid membranes: particle electrophoresis and light scattering study. Biophys Chem. 2004;109:387-97 pubmed
    ..It decreased only when chloroplasts had been incubated with higher Mt concentrations and this effect was better expressed in 'low-salt' than in 'high-salt' thylakoid membranes. ..
  48. Lamb C, Helguero L, Fabris V, Lucas C, Molinolo A, Lanari C. Differential effects of raloxifene, tamoxifen and fulvestrant on a murine mammary carcinoma. Breast Cancer Res Treat. 2003;79:25-35 pubmed
    ..Since raloxifene is under evaluation for use in breast cancer prevention, these results may have important clinical implications. ..
  49. Shin H, Kim J. Melittin selectively activates capsaicin-sensitive primary afferent fibers. Neuroreport. 2004;15:1745-9 pubmed
    ..These results suggest that both melittin and WBV induce nociceptive responses by selective activation of capsaicin-sensitive afferent fibers. ..
  50. Park H, Lee S, Son D, Oh K, Kim K, Song H, et al. Antiarthritic effect of bee venom: inhibition of inflammation mediator generation by suppression of NF-kappaB through interaction with the p50 subunit. Arthritis Rheum. 2004;50:3504-15 pubmed
    ..BV (affinity [K(d)] = 4.6 x 10(-6)M) and melittin (K(d) = 1.2 x 10(-8)M) bound directly to p50. Target inactivation of NF-kappaB by directly binding to the p50 subunit is an important mechanism of the antiarthritic effects of BV. ..
  51. Pan H, Soman N, Schlesinger P, Lanza G, Wickline S. Cytolytic peptide nanoparticles ('NanoBees') for cancer therapy. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2011;3:318-27 pubmed publisher
    ..WIREs Nanomed Nanobiotechnol 2011 3 318-327 DOI: 10.1002/wnan.126 For further resources related to this article, please visit the WIREs website. ..
  52. Zhang L, Kao Y, Qiu W, Wang L, Zhong D. Femtosecond studies of tryptophan fluorescence dynamics in proteins: local solvation and electronic quenching. J Phys Chem B. 2006;110:18097-103 pubmed
    ..These results provide a molecular basis for using tryptophan as a local molecular probe for ultrafast protein dynamics in general. ..
  53. Vuorenoja S, Mohanty B, Arola J, Huhtaniemi I, Toppari J, Rahman N. Hecate-CGbeta conjugate and gonadotropin suppression shows two distinct mechanisms of action in the treatment of adrenocortical tumors in transgenic mice expressing Simian Virus 40 T antigen under inhibin-alpha promoter. Endocr Relat Cancer. 2009;16:549-64 pubmed publisher
    ..If extrapolated to humans, H-CGbeta-c could be considered for the treatment of gonadotropin-dependent adrenal tumors in males, whereas in females gonadotropin suppression, but not H-CGbeta-c, would work better. ..