InterPro domain: IPR011696

This is a family of potent toxins that function as ion-channel inhibitors. Omega-Grammotoxin SIA is a VSCC antagonist that inhibits neuronal N- and P-type VSCC responses [ 1 ]. Huwentoxin-IV, from the Chinese bird spider, is a highly potent neurotoxin that specifically inhibits the neuronal tetrodotoxin-sensitive voltage-gated sodium channel in rat dorsal root ganglion neurons [ 2 ]. Hainantoxin-4, from the venom of spider Selenocosmia hainana, adopts an inhibitor cystine knot structural motif like huwentoin-IV, and is a potent antagonist that acts at site 1 on tetrodotoxin-sensitive (TTX-S) sodium channels [ 3 ]. Study of the molecular nature of toxin-receptor interactions has helped elucidate the functioning of many ion-channels [ 4 ]. Some members of this family, Tap1 and Tap2, can modulate the activity of both voltage-gated sodium and calcium channels which are implicated in the etiology of chronic pain, being interesting for chronic pain treatment [ 5 , 6 ].

1. Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses. Mol. Pharmacol. 44, 451-60
2. Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena. J. Biol. Chem. 277, 47564-71
3. Isolation and characterization of hainantoxin-IV, a novel antagonist of tetrodotoxin-sensitive sodium channels from the Chinese bird spider Selenocosmia hainana. Cell. Mol. Life Sci. 60, 972-8
4. Use of venom peptides to probe ion channel structure and function. J. Biol. Chem. 285, 13315-20
5. A spider-venom peptide with multitarget activity on sodium and calcium channels alleviates chronic visceral pain in a model of irritable bowel syndrome. Pain 176, 1298-1314
6. From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from the spider Cyriopagopus schioedtei. Br J Pharmacol