Brief Biochemistry of Melittin, a Toxin from Bee Venom

One protein structure that I have been wire modelling quite a bit is melittin, a toxin from honey bee (Apis mellifica) venom (examples below):

Melittin is a 26 amino acid peptide made of two alpha helical sections with a nonpolar N-terminus and a polar C-terminus. This structure resembles a bent rod most likely due to proline-14 causing helix destabilization. Given its structure, it is most often studied as a water-soluble tetramer when isolated at high concentrations in bee venom and a monomer at the lowest concentrations known for cell membrane disruption.

To elucidate, the toxicity of melittin on exposed cells comes from biochemical activities that are hardly mentioned in general discussion. As general knowledge, the most prevalent cause of accidental fatalities from bee venom stings results from allergic reactions in hypersensitive people. However, this lethal reaction is the result of phospholipase A2 and in some cases hyaluronidase. There are a myriad of other toxins in bee venom, such as melittin, that are weakly allergenic, yet still cause biochemical aberrations.

Specifically, melittin has the ability to inhibit some Ca(2+)/calmodulin kinases and ion transport pumps such as NA(+)/K(+) ATPase, thus increasing the cell membrane permeability to ions. In addition, negatively charged membrane lipids are an attractant to melittin, thus favoring melittin incorporation into the membrane leading to cell lysis.

Given the aberrant changes in cell structure from this protein, several complex mechanisms have been observed in bees to prevent autolysis by melittin. This protein is derived from a prepromelittin precursor that underwent a 21-amino acid signal peptide cleavage to form promelittin. Further processing occurs after promelittin is secreted into the bee venom sac to protect the bee from the damaging lytic effects of melittin.

P&S

References

Strong, P. N. & Wadsworth, J. D. F. (2000). Chapter 9:  Pharmacologically Active Peptides and Proteins from Bee Venom. In Rochat, H. & Marie-France Martin-Eauclaire M. (Ed. 1) Animal Toxins: Facts and Protocols. (127-151). Basel Switzerland:  Birkhäuser Verlag.

Terwilliger, T. C. & Eisenberg, D. (1981). “The Structure of Melittin” The Journal of Biological Chemistry, 257(11), 6016-22.

Yang, S. & Carrasquer, G. (1997). “Effect of melittin on ion transport across cell membranes”. Zhongguo Yao Li Xue Bao, 18 (1), 3–5.

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