Prediction of 3D Structure of Paralytic Insecticidal Toxin (ITX-1) of Tegenaria agrestis (Hobo Spider)

The hobo spider, Tegenaria agrestis, is a member of the family of spiders known as the Agelenidae or funnel web weavers. The first record of Tegenaria agrestis Walckenaer in the United States was in Seattle,Washington in 1930 [1,2]. European distribution is widespread from Europe to central Asia [3].The current range of T. agrestis, originally named the aggressive house spider, includes Washington, Oregon and Idaho [4] as well as Colorado and southern British Columbia [5] Although no medical concerns are associated with T. agrestis in Europe [6] conjectures have been made in Washington, Oregon and Idaho, since the late 1980s, due the suspicion that its bite causes necrotic tissue lesions. Approximately 500 species of funnel web weavers occur worldwide; about 300 of these are found in North America, and about 100 species are native to Europe. The hobo spider (Tegenaria agrestis) is a member of the genus of spiders known colloquially as funnel web spiders. In the United States, the hobo spider has been considered to be a dangerous species based on a toxicology study on rabbits where lesions appeared after spiders were induced to bite the rabbits, although attempts to replicate the study (by injecting venom to ensure envenomation) have failed to produce necrotic lesions [7,8]. Many peptide toxins from spider venoms share structural features, amino acid composition and consensus sequences that allow them to interact with related classes of cellular receptors. They have become increasingly useful agents for the study of voltage-sensitive and ligand-gated ion channels and the discrimination of their cellular subtypes. Spider peptide toxins have also been recognized as useful agents for their antimicrobial properties and the study of pore formation in cell membranes. Their high insecticidal potency can also make them useful probes for the discovery of novel insecticide targets in the insect nervous system or for the development of genetically engineered microbial pesticides. Insecticidal peptides from Tegenaria agrestis spider venom may have a direct effect on the insect central nervous system. Fractionation of venom from an agelenid spider, Tegenaria agrestis, resulted in the isolation of a family of three peptides with potent insecticidal activity. These peptide toxins, ITX-1, ITX -2, and ITX -3, whose sequences were revealed from cloned cDNAs, each consist of 50-60 amino acid residues, six of which are cysteines [9]. One peptide and ten acylpolyamine toxins (curtatoxins) were purified and identified from venom of Hololena curta [10]. Acylpolyamines represent the vast majority of organic components from the spider venom. Acylpolyamine analogues have proven to suppress hippocampal epileptic discharges. Acylpolyamines and peptides from spider venoms represent an interesting source of molecules for the design of novel pharmaceutical drugs [11].