8.B.12 The Spider Toxin (STx2) Family

Phoneutria nigriventer toxins, PnTx2-5 and PnTx2-6, markedly delay the fast inactivation kinetics of neuronal-type sodium channels, but they have differences in their interactions with the channel (Matavel et al., 2009). PnTx2-6 has an affinity 6 times higher than that of PnTx2-5, and its effects are not reversible within 10-15 min of washing. PnTx2-6 partially (59%) competes with the scorpion alpha-toxin AaHII, but not with the scorpion beta-toxin CssIV, thus suggesting a mode of action similar to that of site 3 toxins. However, PnTx2-6 is not removed by strong depolarizing pulses, as in the known site 3 toxins. Matavel et al., 2009 also established that the cysteines in these poorly helical toxins are in their oxidized form.



This family belongs to the Huwentoxin Superfamily.

 

References:

Liu, Z., J. Dai, L. Dai, M. Deng, Z. Hu, W. Hu, and S. Liang. (2006). Function and solution structure of Huwentoxin-X, a specific blocker of N-type calcium channels, from the Chinese bird spider Ornithoctonus huwena. J. Biol. Chem. 281: 8628-8635.

Matavel, A., C. Fleury, L.C. Oliveira, F. Molina, M.E. de Lima, J.S. Cruz, M.N. Cordeiro, M. Richardson, C.H. Ramos, and P.S. Beirão. (2009). Structure and activity analysis of two spider toxins that alter sodium channel inactivation kinetics. Biochemistry 48: 3078-3088.

Souza, A.H., J. Ferreira, M.d.o.N. Cordeiro, L.B. Vieira, C.J. De Castro, G. Trevisan, H. Reis, I.A. Souza, M. Richardson, M.A. Prado, V.F. Prado, and M.V. Gomez. (2008). Analgesic effect in rodents of native and recombinant Ph alpha 1beta toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom. Pain 140: 115-126.

Vieira, L.B., C. Kushmerick, H.J. Reis, C.R. Diniz, M.N. Cordeiro, M.A. Prado, E. Kalapothakis, M.A. Romano-Silva, and M.V. Gomez. (2003). PnTx3-6 a spider neurotoxin inhibits K+-evoked increase in [Ca2+](i) and Ca2+-dependent glutamate release in synaptosomes. Neurochem Int 42: 277-282.

Vieira, L.B., C. Kushmerick, M.E. Hildebrand, E. Garcia, A. Stea, M.N. Cordeiro, M. Richardson, M.V. Gomez, and T.P. Snutch. (2005). Inhibition of high voltage-activated calcium channels by spider toxin PnTx3-6. J Pharmacol Exp Ther 314: 1370-1377.

Examples:

TC#NameOrganismal TypeExample
8.B.12.1.1The spider toxin Tx2-5 (Matavel et al., 2009).

Spiders

Tx2-5 of Phoneutria nigriventer (P29424)

 
8.B.12.1.2

Omega-ctenitoxin-Pn4a, CnTx-Pn4a; neurotoxin Tx3-6; α1-β toxin of 90 aas

Animals

Tx3.6 of Phoneutria nigriventer

 
8.B.12.1.3

Hainantoxin XV-2, HnTx-XV-2 of 117 aas.

Spiders

HnTx-XV-2 of Haplopelma hainanum

 
8.B.12.1.4

Cystine knot toxin of 114 aas

Spiders

Cystine knot toxin of Dolomedes mizhoanus

 
8.B.12.1.5

Omega-ctenitoxin-Pn4a of 90 aas and 1 TMS.  The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. It is a potent blocker of high voltage-activated calcium channels, acting mainly on P/Q-type (Cav2.1/CACNA1A) calcium channels and with a minor effect on L- (Cav1/CACNA1) and N-type (Cav2.2/CACNA1B) calcium channels (Vieira et al. 2005). It blocks glutamate release in synaptic transmission mediated by calcium channels (Vieira et al. 2003). The toxin also inhibits the KCl-induced increase of intrasynaptosomal free calcium (Souza et al. 2008).

Toxin of Phoneutria nigriventer (Brazilian armed spider)

 
Examples:

TC#NameOrganismal TypeExample