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).
Ω-agatoxin IVA of Agelenopsis aperta (P30288)
Mu-agatoxin II (37aas)
Mu-agatoxin II of Agelenopsis aperta (P11058)
Mu-agatoxin-Hc1a (Curtatoxin-1) (36aas)
Curtatoxin-1 of Hololena curta (P15967)
U10-Ctenitoxin-Co1a of 37 aas (Trachsel et al. 2012).
Ctentitoxin of Ctenus ornatus (Oligoctenus ornatus; brazilian spider)
Putative toxin of 148 aas
Putative toxin of Tribolium castaneum (red flour beetle)
U3-Agatoxin Ao1h of 69 aas
Agatoxin of Agelena orientalis
U2-agatoxin Ao1k of 69 aas. Insect active toxin causing rapid but reversible paralysis in crickets. No activity shown in mammals. Does not show effect on mammalian voltage-gated calcium channels.
Agatoxin of Agelena orientalis
Tachystatin-B1 of 42 aas. Exhibits stronger antimicrobial activity against Gram-positive bacteria (S. aureus (IC50 is 7.4 µg/ml)), fungi (C. albicans (IC50 is 3.0 µg/ml) and P. pastoris (IC50 is 0.1 µg/ml)) than Gram-negative bacteria (E.coli, no inhibition at 100 µg/ml). Binds to chitin. Does not cause hemolysis on sheep erythrocytes. Has no blocking activity on the P-type calcium channel.
Tachystatin of Tachypleus tridentatus (Japanese horseshoe crab)
Delta atracotoxin-Hv1a (Versutoxin) (42aas) (NMR structure available (1VTXA)). Antagonist of insect voltage-gated calcium channels (Chong et al., 2007; Khan et al., 2006; Wang et al., 1999) as well as sodium channels (Luch 2010).
Versutoxin of Hadronyche versuta (P13494)
Delta hexatoxin-Mg1a; Neurotoxin Magi-4 (105aas). Targets sites 3 and 4 of mammalian Na+ channels; slows inactivation (Yamaji et al., 2009).
Neurotoxin Magi-4 of Macrothele gigas (P83560)
U17-barytoxin-Tl1a; U17-BATX-Tl1a; Toxin ICK-35 of 114 aas.
U17-BATX-TI1a of Trittame loki