Structure and function of insecticidal neurotoxins from Australian funnel-web spiders

Insect pests decimate a significant proportion of the world's food supply and transmit a number of deadly human diseases. These arthropods are generally controlled by spraying broadspectrum chemical insecticides. However, the emergence of insecticide-resistant insect populations, as well as increasing disquiet about the environmental and human health risks associated with certain agrochemicals, has stimulated the search for new arthropod-control strategies. Since the primary role of spider venoms is to kill or immobilize arthropod prey, it is not surprising that spider venoms have proved to be rich sources of insecticidal compounds. In this review we examine the function and three-dimensional structure of four families of novel insecticidal neurotoxins that have been isolated from the venom of Australian funnel-web spiders. Although all of these toxins are members of the inhibitor cystine-knot family, they have proved to be structural chameleons, with the three-dimensional fold often providing few clues about toxin function. However, significant progress is being made in identifying the targets and mapping the bioactive surfaces of these peptides. In addition to being useful lead compounds for insecticide design, these neurotoxins should provide valuable tools for the pharmacological and structural characterization of insecticide targets.