Heteropodatoxin

Heteropodatoxins are peptide toxins from the venom of the giant crab spider Heteropoda venatoria, which block Kv4.2 voltage-gated potassium channels.

Solution structure of heteropodatoxin-2. PDB entry 1emx [1]

Sources

Heteropodatoxins are purified from the venom of the giant crab spider, Heteropoda venatoria.[2]

Chemistry

Heteropodatoxins contain an Inhibitor Cystine Knot (ICK) motif, which consist of a compact disulfide-bonded core, from which four loops emerge.[1] There are three different heteropodatoxins:[2]

  • 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.[2] They show sequence similarity to Hanatoxins, which can be isolated from the venom of the Chilean rose tarantula Grammostola rosea.[2]

Target

Heteropodatoxins block A-type, transient voltage-gated potassium channels. All three toxins have been shown to block the potassium channel Kv4.2.[2] Recombinant heteropodatoxin-2 blocks the potassium channels Kv4.1, Kv4.2 and Kv4.3, but not Kv1.4, Kv2.1, or Kv3.4.[3]

Mode of action

Heterpodatoxin-2 most likely acts as a gating modifier of the Kv4.2 channels.[3] 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,[3] and a role as a pore blocker cannot be excluded.[1] 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.[2]

Toxicity

The giant crab spider can cause a locally painful bite.[4]

References
  1. Bernard et al. (2000).
  2. Sanguinetti et al. (1997).
  3. Zarayskiy et al. (2005).
  4. Edwards, G. B. (2009). "huntsman spider - Heteropoda venatoria (Linnaeus)". Featured Creatures. Retrieved May 11, 2009.

Bibliography
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