Drosomycin, an innate immunity peptide of Drosophila melanogaster, interacts with the fly voltage-gated sodium channel

J Biol Chem. 2009 Aug 28;284(35):23558-63. doi: 10.1074/jbc.M109.023358. Epub 2009 Jul 1.


Several peptide families, including insect antimicrobial peptides, plant protease inhibitors, and ion channel gating modifiers, as well as blockers from scorpions, bear a common CSalphabeta scaffold. The high structural similarity between two peptides containing this scaffold, drosomycin and a truncated scorpion beta-toxin, has prompted us to examine and compare their biological effects. Drosomycin is the most expressed antimicrobial peptide in Drosophila melanogaster immune response. A truncated scorpion beta-toxin is capable of binding and inducing conformational alteration of voltage-gated sodium channels. Here, we show that both peptides (i) exhibit anti-fungal activity at micromolar concentrations; (ii) enhance allosterically at nanomolar concentration the activity of LqhalphaIT, a scorpion alpha toxin that modulates the inactivation of the D. melanogaster voltage-gated sodium channel (DmNa(v)1); and (iii) inhibit the facilitating effect of the polyether brevetoxin-2 on DmNa(v)1 activation. Thus, the short CSalphabeta scaffold of drosomycin and the truncated scorpion toxin can maintain more than one bioactivity, and, in light of this new observation, we suggest that the biological role of peptides bearing this scaffold should be carefully examined. As for drosomycin, we discuss the intriguing possibility that it has additional functions in the fly, as implied by its tight interaction with DmNa(v)1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / immunology
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / pharmacology
  • Drosophila melanogaster / chemistry
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / immunology
  • Drosophila melanogaster / metabolism*
  • Fungi / drug effects
  • Immunity, Innate
  • Molecular Sequence Data
  • Potassium Channels, Voltage-Gated / chemistry
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*
  • Protein Binding
  • Sequence Alignment


  • Drosophila Proteins
  • Potassium Channels, Voltage-Gated
  • DRS protein, Drosophila