Huwentoxin
Huwentoxins (HWTX) are a group of neurotoxic peptides found in the venom of the Chinese bird spider Haplopelma schmidti. The species was formerly known as Haplopelma huwenum, Ornithoctonus huwena and Selenocosmia huwena. While structural similarity can be found among several of these toxins, HWTX as a group possess high functional diversity.
Huwentoxins are neurotoxic peptides produced by the Chinese bird spider, Haplopelma schmidti.
The venom of H. schmidti contains a large variety of neurotoxins, which function to paralyze the spider's prey. So far, 14 of the isolated primarily neurotoxic peptide components have been characterized and investigated. In the following, two subfamilies of the HWTX are described: those targeting voltage-gated calcium channels, and those targeting voltage-gated sodium channels.
HWTX-I is the most abundant toxic component in the venom of H. schmidti. It inhibits presynaptic N-type Ca2+ channels.
The molecular weight of HWTX-I is 3750 Da. The toxin comprises 33 residues, including six cysteines that form three disulfide linkages. These were assigned as Cys2-Cys17, Cys9-Cys22, and Cys16-Cys29 and are buried within the molecule. The molecule adopts a compact structure consisting of a small triple-stranded antiparallel beta-sheet and five beta-turns. It was found that the structure contains an inhibitor cystine knot (ICK) motif. To form this motif, three disulfide bridges are needed. Two of them create a loop through which the third disulfide bridge passes. The structure of HWTX-I is very stable, secondary structure elements do not significantly alter under different pH conditions or after heating.
HWTX-I selectively inhibits N-type HVA channels. A recent study found that HWTX-I also inhibits Na+ channels.
In mice the intraperitoneal LD50 of HWTX-I is 0.70 mg/kg, the intracisternal LD50 has been determined as 9.40 µg/kg. Neurotoxic symptoms after intraperitoneal injection were gasping, excitation, spastic paralysis of the hindlimb and asynergia.
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