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In-silico homology modeling of three isoforms of insect defensins from the dengue vector mosquito, Aedes aegypti (Linn., 1762)

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Abstract

Dengue is a serious public health problem in tropical and subtropical countries. It is caused by any of the four serologically distinct dengue viruses, namely DENV1–4. The viruses are transmitted by Aedes mosquitoes. Understanding various defence mechanisms of insects has become a prime area of research worldwide. In insects, the first line of defence against invading pathogens includes cellular mechanisms and a battery of antimicrobial peptides such as defensins, cecropins etc. Defensins—cationic, cysteine-rich peptides consisting of ∼40 amino acids with broad-spectrum activity against Gram-positive bacteria—have been reported from a wide range of organisms. In the dengue vector mosquito, Aedes aegypti, three isoforms of defensins are reported to be expressed in a spatial and temporal fashion. This report presents the three-dimensional structures of the three isoforms of Ae. aegypti defensins predicted by comparative modeling. Prediction was done with Modeller 9v1 and the structures validated through a series of tests. The best results of the prediction study are presented, and may help lead to the discovery of new synthetic peptides or derivatives of defensins that could be useful in the control of vector-borne diseases.

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References

  1. Halstead SB (2007) Dengue. Lancet 370:1644–1652. doi:10.1016/S0140-6736(07)61687-0

    Article  Google Scholar 

  2. Gubler DJ (1998) Dengue and dengue haemorrhagic fever. Clin Microbiol Rev 11:480–496

    CAS  Google Scholar 

  3. Thenmozhi V, Hiriyan J, Tewari SC, Samuel PP, Paramasivan R, Rajendran R et al (2007) Natural vertical transmission of dengue virus in Aedes albopictus (Diptera: Culicidae) in Kerala, a Southern Indian state. Jpn J Infect Dis 60:245–249

    Google Scholar 

  4. Enserink M (2008) ENTOMOLOGY: a mosquito goes global. Science 320:954b. doi:10.1126/science.320.5878.954b. doi:10.1126/science.320.5878.864

    Article  Google Scholar 

  5. Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning M et al (2007) Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 370:1840–1846. doi:10.1016/S0140-6736(07)61779-6

    Article  CAS  Google Scholar 

  6. Chakravarthi A, Kumaria R (2005) Eco-epidemiological analysis of dengue infection during an outbreak of dengue fever, India. Virol J 2:32. doi:10.1186/1743-422X-2-32

    Article  Google Scholar 

  7. Hoffmann JA, Kafatos FC, Janeway CA Jr, Ezekowitz RAB (1999) Phylogenetic perspectives in innate immunity. Science 248:1313–1318. doi:10.1126/science.284.5418.1313

    Article  Google Scholar 

  8. Brogden KA (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria. Nat Rev Microbiol 3:238–241. doi:10.1038/nrmicro1098

    Article  CAS  Google Scholar 

  9. Lowenberger C (2001) Innate immune responses of Aedes aegypti. Insect Biochem Mol Biol 31:219–229. doi:10.1016/S0965-1748(00)00141-7

    Article  CAS  Google Scholar 

  10. Leippe M (1999) Antimicrobial and cytolytic polypeptides of amoeboid protozoa–effector molecules of primitive phagocytes. Dev Comp Immunol 23:267–279. doi:10.1016/S0145-305X(99)00010-5

    Article  CAS  Google Scholar 

  11. Lambert J, Keppi E, Dimarcq J-L, Wicker C, Reichhart J-M, Dunbar B et al (1989) Insect immunity: isolation from immune blood of the dipteran Phormia terranovae of two insect antibacterial peptides with sequence homology to rabbit lung macrophage bactericidal peptides. Proc Natl Acad Sci USA 86:262–266. doi:10.1073/pnas.86.1.262

    Article  CAS  Google Scholar 

  12. Chalk R, Albuquerque CM, Ham PJ, Townson H (1995) Full sequence and characterization of two insect defensins: immune peptides from the mosquito Aedes aegypti. Proc R Soc Lond B Biol Sci 261(1361):217–221. doi:10.1098/rspb.1995.0139

    Article  CAS  Google Scholar 

  13. Lowenberger C, Bulet P, Charlet M, Hetru C, Hodgeman B, Christensen BM et al (1995) Insect immunity: isolation of three novel inducible antibacterial defensins from the vector mosquito, Aedes aegypti. Insect Biochem Mol Biol 25(7):867–873. doi:10.1016/0965-1748(95)00043-U

    Article  CAS  Google Scholar 

  14. Wade D, Boman A, Wahlin B, Drain CM, Andreu D, Boman HG et al (1990) All-D amino acid-containing channel-forming antibiotic peptides. Proc Natl Acad Sci USA 88:4761–4765. doi:10.1073/pnas.87.12.4761

    Article  Google Scholar 

  15. Cociancich S, Ghazi A, Hetru C, Hoffmann JA, Letelliers L (1993) Insect defensin, an inducible antibacterial peptid forms voltage-dependent channels in Micrococcus luteus. J Biol Chem 268(26):19239–19245

    CAS  Google Scholar 

  16. Paramasivan R, Sivaperumal R, Dhananjeyan KJ, Thenmozhi V, Tyagi BK (2007) Prediction of 3-dimentional structure of salivary odorant binding protein-2 of Culex quinquefasciatus. In Silico Biol 7:1–6

    CAS  Google Scholar 

  17. Pham DQ-D (2000) Molecular modeling of insect ferritins. In Silico Biol 2:S31–44

    Google Scholar 

  18. Krishna Murthy HM, Clum S, Padmanabhan R (1999) Dengue virus NS3 serine protease. J Biol Chem 274(9):5573–5580. doi:10.1074/jbc.274.9.5573

    Article  Google Scholar 

  19. Brinkworth RI, Fairlie DP, Leung D, Young PR (1999) Homology model of the dengue 2 virus NS3 protease: putative interactions with both substrate and NS2B cofactor. J Gen Virol 80:1167–1177

    CAS  Google Scholar 

  20. Nall TA, Chappell KJ, Stoermer MJ, Fang N-X, Tyndall JDA, Young PR et al (2004) Enzymatic characterization and homology model of a catalytically active recombinant West Nile Virus NS3 protease. J Biol Chem 279(47):48535–48542. doi:10.1074/jbc.M406810200

    Article  CAS  Google Scholar 

  21. Chappell KJ, Nall TA, Stoermer MJ, Fang N-X, Tyndall JDA, Fairlie DP et al (2005) Site-directed mutagenesis and kinetic studies of the West Nile Virus NS3 protease identify key enzyme-substrate interactions. J Biol Chem 280(4):2896–2903. doi:10.1074/jbc.M409931200

    Article  CAS  Google Scholar 

  22. Vijayasri S, Agrawal S (2005) Domain based homology modeling and mapping of the conformational epitopes of envelope glycoprotein of West Nile virus. J Mol Model 11(3):248–255. doi:10.1007/s00894-005-0272-7

    Article  CAS  Google Scholar 

  23. Zhou H, Singh NJ, Kim KS (2006) Homology modeling and molecular dynamics study of West Nile Virus NS3 protease: A molecular basis for the catalytic activity increased by the NS2B cofactor. Proteins 65:692–701. doi:10.1002/prot.21129

    Article  CAS  Google Scholar 

  24. Baker D, Sali A (2001) Protein Structure Prediction and Structural Genomics. Science 294:93–96. doi:10.1126/science.1065659

    Article  CAS  Google Scholar 

  25. Schibli DJ, Hunter HN, Aseyev V, Starner TD, Wiencek JM, McCray Jr. PB, Tack BF, Vogel HJ (2002) The solution structures of the human beta-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus. J Biol Chem 277:8279–8289

    Google Scholar 

  26. Cociancich S, Clarke DJ, Polfer NC, Barran PE, Langley RJ, Govan JRW et al (2004) Structure-activity relationships in defensin dimers. J Biol Chem 279(47):48671–48679. doi:10.1074/jbc.M404690200

    Article  CAS  Google Scholar 

  27. Suresh A, Verma C (2006) Modelling study of dimerization in mammalian defensins. BMC Bioinformatics 7(Suppl 5):S17. doi:10.1186/1471-2105-7-S5-S17

    Article  CAS  Google Scholar 

  28. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    CAS  Google Scholar 

  29. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680. doi:10.1093/nar/22.22.4673

    Article  CAS  Google Scholar 

  30. Higgins DG, Thompson JD, Gibson TJ (1996) Using CLUSTAL for multiple sequence alignments. Methods Enzymol 266:383–402. doi:10.1016/S0076-6879(96)66024-8

    Article  CAS  Google Scholar 

  31. Felsentein J (2004) PHYLIP (Phylogeny Inference Package) version 3.6. Distributed by the author. Department of Genomic Studies, University of Washington, Seattle.

    Google Scholar 

  32. Jones DT, Taylor WR, Thornton JM (1992) The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci 8:275–282

    CAS  Google Scholar 

  33. Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234:779–815. doi:10.1006/jmbi.1993.1626

    Article  CAS  Google Scholar 

  34. Marti-Renom MA, Stuart A, Fiser A, Sánchez R, Melo F, Sali A (2000) Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct 29:291–325. doi:10.1146/annurev.biophys.29.1.291

    Article  CAS  Google Scholar 

  35. Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Cryst 26:283–291. doi:10.1107/S0021889892009944

    Article  CAS  Google Scholar 

  36. Godzik A, Kolinski A, Skolnick J (1995) Are proteins ideal mixtures of amino acids? Analysis of energy parameter sets. Protein Sci 4(10):2107–2117

    Article  CAS  Google Scholar 

  37. Godzik A (1996) Knowledge-based potentials for protein folding: what can we learn from known protein structures? Structure 4(4):363–366. doi:10.1016/S0969-2126(96)00041-X

    Article  CAS  Google Scholar 

  38. Pawlowski K, Jaroszewski L, Bierzynski A, Godzik A (1997) Multiple model approach-dealing with alignment ambiguities in protein modeling. Pac Symp Biocomput 1997:328–339

  39. Jaroszewski L, Pawlowski K, Godzik A (1998) Multiple model approach: exploring the limits of comparative modeling. J Mol Model 4:294–309. doi:10.1007/s008940050087

    Article  CAS  Google Scholar 

  40. Cornet B, Bonmatin JM, Hetru C, Hoffmann JA, Ptak M, Vovelle F (1995) Refined three-dimensional solution structure of insect defensin A. Structure 3:435–448. doi:10.1016/S0969-2126(01)00177-0

    Article  CAS  Google Scholar 

  41. Hanzawa H, Shimada I, Kuzuhara T, Komano H, Kohda D, Inagaki F et al (1990) 1H nuclear magnetic resonance study of the solution conformation of an antibacterial protein, sapecin. FEBS Lett 269:413–420. doi:10.1016/0014-5793(90)81206-4

    Article  CAS  Google Scholar 

  42. DeLano WL (2002) The PyMOL molecular graphics system. DeLano, San Carlos, CA

    Google Scholar 

  43. Krieger E, Nabuurs SB, Vriend G (2003) Homology modeling. In: Bourne PE, Weissig H (eds) Structural bioinformatics. Wiley-Liss, New York, pp 507–521

    Google Scholar 

  44. Hancock REW, Chapple DS (1999) Peptide antibiotics. Antimicrob Agents Chemother 43:1317–1323

    CAS  Google Scholar 

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Correspondence to K. J. Dhananjeyan.

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Dhananjeyan, K.J., Sivaperumal, R., Paramasivan, R. et al. In-silico homology modeling of three isoforms of insect defensins from the dengue vector mosquito, Aedes aegypti (Linn., 1762). J Mol Model 15, 507–514 (2009). https://doi.org/10.1007/s00894-008-0408-7

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