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8.B.6 The Ca2+Channel-targeting Spider Toxin (CST) Family

A novel polypeptide, designated omega-Lsp-IA, which modulates P-type Ca2+ channels, has been purified from the venom of the spider Geolycosa sp. omega-Lsp-IA contains 47 amino acid residues and 4 intramolecular disulfide bridges (Pluzhnikov et al., 2007). It belongs to a group of spider toxins affecting Ca2+ channels and may form the inhibitor cystine knot (ICK) fold. A cluster of positively charged residues in the C-terminal loop of the peptide and a regular distribution of hydrophobic residues may play a role in its mechanism of action. At saturating concentration (10nM), the peptide clearly slows down the activation kinetics and partially inhibits the amplitude of P-current in rat cerebellar Purkinje neurons. Prominent deceleration of the activation kinetics is manifested as the appearance of a five-fold slower component of the current activation. Omega-Lsp-IA shows differing effects on different Ca2+ channel types. Omega-Agatoxin IVA completely removed the effect of omega-Lsp-IA on the whole-cell Ca2+ current. Omega-Lsp-IA appears to act specifically on P-type Ca2+channels (Pluzhnikov et al., 2007). 

δ-atracotoxin isoforms (δ-ACTX; 8.B.6.3.1) bind to voltage-gated sodium channels in the same way as classical scorpion alpha-toxins. According to the 'voltage-sensor trapping model', delta-ACTX isoforms interact with the voltage sensor S4 transmembrane segment of alpha-subunit domain IV, thereby preventing its normal outward movement and concurrent conformational changes required for inactivation of the channel. As a consequence, prolonged action potentials at autonomic or somatic synapses induce massive transmitter release, resulting in clinical correlates of neuroexcitation (e.g., muscle fasciculation, spasms, paresthesia, tachycardia and diaphoresis) (Luch 2010).

This family belongs to the: Huwentoxin Superfamily.

References associated with 8.B.6 family:

Chong, Y., J.L. Hayes, B. Sollod, S. Wen, D.T. Wilson, P.G. Hains, W.C. Hodgson, K.W. Broady, G.F. King, and G.M. Nicholson. (2007). The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Biochem Pharmacol 74: 623-638. 17610847
Khan, S.A., Y. Zafar, R.W. Briddon, K.A. Malik, and Z. Mukhtar. (2006). Spider venom toxin protects plants from insect attack. Transgenic Res 15: 349-357. 16779650
Luch, A. (2010). Mechanistic insights on spider neurotoxins. EXS. 100: 293-315. 20358687
Pluzhnikov, K., A. Vassilevski, Y. Korolkova, A. Fisyunov, O. Iegorova, O. Krishtal, and E. Grishin. (2007). omega-Lsp-IA, a novel modulator of P-type Ca2+ channels. Toxicon. 50: 993-1004. 17888477
Trachsel, C., D. Siegemund, U. Kämpfer, L.S. Kopp, C. Bühr, J. Grossmann, C. Lüthi, M. Cunningham, W. Nentwig, L. Kuhn-Nentwig, S. Schürch, and J. Schaller. (2012). Multicomponent venom of the spider Cupiennius salei: a bioanalytical investigation applying different strategies. FEBS J. 279: 2683-2694. 22672445
Wang, X., R. Smith, J.I. Fletcher, H. Wilson, C.J. Wood, M.E. Howden, and G.F. King. (1999). Structure-function studies of omega-atracotoxin, a potent antagonist of insect voltage-gated calcium channels. Eur J Biochem 264: 488-494. 10491095
Yamaji, N., M.J. Little, H. Nishio, B. Billen, E. Villegas, Y. Nishiuchi, J. Tytgat, G.M. Nicholson, and G. Corzo. (2009). Synthesis, solution structure, and phylum selectivity of a spider δ-toxin that slows inactivation of specific voltage-gated sodium channel subtypes. J. Biol. Chem. 284: 24568-24582. 19592486