Heteropodatoxin

Heteropodatoxins are purified from the venom of the giant crab spider, Heteropoda venatoria (Sanguinetti et al. 1997).

Heteropodatoxins contain an Inhibitor Cystine Knot (ICK) motif, which consist of a compact disulfide-bonded core, from which four loops emerge (Bernard et al. 2000). There are three different heteropodatoxins (Sanguinetti et al. 1997):

• heteropodatoxin-1, also known as Toxin AU3/KJ5 or HpTx1
• heteropodatoxin-2, also known as Toxin KJ6 or HpTx2
• heteropodatoxin-3, also known as Toxin AU5C/KJ7 or HpTx3

These three toxins are structurally similar peptides of 29-32 amino acids (Sanguinetti et al. 1997). They show sequence similarity to Hanatoxins, which can be isolated from the venom of the Chilean rose tarantula Grammostola rosea (Sanguinetti et al. 1997).

Heteropodatoxins block A-type, transient voltage-gated potassium channels. All three toxins have been shown to block the potassium channel Kv4.2 (Sanguinetti et al. 1997). Recombinant heteropodatoxin-2 blocks the potassium channels Kv4.1, Kv4.2 and Kv4.3, but not Kv1.4, Kv2.1, or Kv3.4 (Zarayskiy et al. 2005).

Heterpodatoxin-2 most likely acts as a gating modifier of the Kv4.2 channels (Zarayskiy et al. 2005). It shifts the voltage dependence of the activation and the inactivation of the Kv4.3 potassium channel to more positive values. As a result, in the presence of the toxin this channel has a higher probability of being inactivated and a larger depolarization is needed to open the channel. However, heterpodatoxin-2 did not affect the voltage dependence of the Kv4.1 channel, suggesting that the precise mechanism of block remains to be elucidated (Zarayskiy et al. 2005) and a role as a pore blocker cannot be excluded (Bernard et al. 2000). The voltage dependence of Kv4.2 block varies among the three different heteropodatoxins. It is less voltage dependent for HpTx1 than for HpTx2 or HpTx3 (Sanguinetti et al. 1997).

The giant crab spider can cause a locally painful bite.[1]

• Bernard C, Legros C, Ferrat G, Bischoff U, Marquardt A, Pongs O, Darbon H (2000). "Solution structure of hpTX2, a toxin from Heteropoda venatoria spider that blocks Kv4.2 potassium channel". Protein Sci. 9 (11): 2059–67. PMC 2144494. PMID 11152117.{{cite journal}}: CS1 maint: ref duplicates default (link)
• Sanguinetti MC, Johnson JH, Hammerland LG, Kelbaugh PR, Volkmann RA, Saccomano NA, Mueller AL (1997). "Heteropodatoxins: peptides isolated from spider venom that block Kv4.2 potassium channels". Mol. Pharmacol. 51 (3): 491–8. PMID 9058605.{{cite journal}}: CS1 maint: ref duplicates default (link)
• Zarayskiy VV, Balasubramanian G, Bondarenko VE, Morales MJ (2005). "Heteropoda toxin 2 is a gating modifier toxin specific for voltage-gated K+ channels of the Kv4 family". Toxicon. 45 (4): 431–42. doi:10.1016/j.toxicon.2004.11.015. PMID 15733564.{{cite journal}}: CS1 maint: ref duplicates default (link)