Heteropodatoxin

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Solution structure of heteropodatoxin-2. PDB entry Template:PDBe Template:Sfnp

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

Sources

Heteropodatoxins are purified from the venom of the giant crab spider, Heteropoda venatoria.Template:Sfnp

Chemistry

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

• 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.Template:Sfnp They show sequence similarity to Hanatoxins, which can be isolated from the venom of the Chilean rose tarantula Grammostola rosea.Template:Sfnp

Target

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

Mode of action

Heterpodatoxin-2 most likely acts as a gating modifier of the Kv4.2 channels.Template:Sfnp 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,Template:Sfnp and a role as a pore blocker cannot be excluded.Template:Sfnp 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.Template:Sfnp

Toxicity

The giant crab spider can cause a locally painful bite.