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8.B.21 The Spider Insecticidal Neurotoxin Cyrtautoxin (Cyrautoxin) Family

One of the most potent insecticidal venom peptides described to date is Aps III from the venom of the trapdoor spider, Apomastus schlingeri. Aps III is highly neurotoxic to lepidopteran crop pests, making it a promising candidate for bioinsecticide development. Skinner et al. 1992 showed that recombinant Aps III (rAps III) is an atypical knottin peptide; three of the disulfide bridges form a classical inhibitor cystine knot motif while the fourth disulfide acts as a molecular staple that restricts the flexibility of an unusually large β-hairpin loop that often houses the pharmacophore in this class of toxins. The irreversible paralysis induced in insects by rAps III results from a potent block of insect voltage-gated sodium channels. Channel block by rAps III is voltage-independent insofar as it occurs without significant alteration in the voltage-dependence of channel activation or steady-state inactivation. Thus, rAps III appears to be a pore blocker that plugs the outer vestibule of insect voltage-gated sodium channels. This mechanism of action contrasts strikingly with virtually all other sodium channel modulators isolated from spider venoms that act as gating modifiers by interacting with one or more of the four voltage-sensing domains of the channel (Skinner et al. 1992).

This family belongs to the: Conotoxin Superfamily.

References associated with 8.B.21 family:

Chen, J., M. Deng, Q. He, E. Meng, L. Jiang, Z. Liao, M. Rong, and S. Liang. (2008). Molecular diversity and evolution of cystine knot toxins of the tarantula Chilobrachys jingzhao. Cell Mol Life Sci 65: 2431-2444. 18581053
Fan, C.X., X.K. Chen, C. Zhang, L.X. Wang, K.L. Duan, L.L. He, Y. Cao, S.Y. Liu, M.N. Zhong, C. Ulens, J. Tytgat, J.S. Chen, C.W. Chi, and Z. Zhou. (2003). A novel conotoxin from Conus betulinus, kappa-BtX, unique in cysteine pattern and in function as a specific BK channel modulator. J. Biol. Chem. 278: 12624-12633. 12547831
Robinson, S.D. and R.S. Norton. (2014). Conotoxin gene superfamilies. Mar Drugs 12: 6058-6101. 25522317
Skinner, W.S., P.A. Dennis, J.P. Li, and G.B. Quistad. (1992). Identification of insecticidal peptides from venom of the trap-door spider, Aptostichus schlingeri (Ctenizidae). Toxicon 30: 1043-1050. 1440641