Hainantoxin

Hainantoxins (HNTX) are neurotoxins from the venom of the Chinese bird spider Haplopelma hainanum. Hainantoxins specifically inhibit tetrodotoxin-sensitive Voltage-gated sodium channels, thereby causing blockage of neuromuscular transmission and paralysis. Currently, 13 different hainantoxins are known (HNTX-I – HNTX-XIII), but only HNTX-I, -II, -III, -IV and -V have been investigated in detail.

HNTX-I, HNTX-III, HNTX-IV and HNTX-V are made by the Chinese bird spider Haplopelma hainanum (=Ornithoctonus hainana, Selenocosmia hainana).

Hainantoxins I, III, IV and V show high homology, including the presence of three disulfide bonds that form an inhibitor cysteine knot (ICK) motif.

The main component of the venom of O. hainana is HNTX-I. It has 33 amino acid residues, with a total molecular weight of 3605-3608 Da. HNTX-I contains a short triple-stranded anti-parallel beta-sheet and four beta-turns. The amino acid residues His28 and Asp26 are needed for the bioactivity of HNTX-I.

HNTX-II has a molecular weight of 4253 Da and contains 37 amino acid residues. The complete amino acid sequence of HNTX-II is NH2-LFECSV SCEIEK EGNKD CKKKK CKGGW KCKFN MCVKV-COOH.

The structure of HNTX-III consists of 33-35 amino acid residues, which form a beta-sheet with connections between Asp7 and Cys9, Tyr21 and Ser23, and Lys27 and Val30.

HNTX-IV has 35 amino acid residues with a total molecular weight of 3989 Da. The first strand consists of an antiparallel beta-sheet. The complete amino acid sequence of HNTX-IV is NH2-ECLGFG KGCNPS NDQCCK SSNLVC SRKHRW CKYEI-CONH2. Lys 27, His28, Arg29 and Lys 32 are the neuroactive amino acid residues.

HNTX-V consists of 35 amino acid residues. The whole amino acid residue sequence of HNTX-V is NH2-ECLGFG KGCNPS NDQCCK SANLVC SRKHRW CKYEI-COOH. At the active binding site of HNTX-V, Lys27 and Arg 29 are the most important.

Hainantoxins selectively inhibit tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels (VGSCs). Voltage-gated Ca2+ channels (VGCCs), tetrodotoxin-resistant (TTX-R) VGSCs and rectifier-delayed potassium channels are not affected. HNTX-III and HNTX-IV are part of the Huwentoxin-I family. Toxins from the Huwentoxin-I family are thought to bind to site 1 on the sodium channels. Other hainantoxins bind at site 3 of the sodium channels. HNTX-I specifically blocks mammalian Nav1.2 and insect para/tipE channels expressed in Xenopus laevis oocytes. HNTX-I is a weak antagonist of the vertebrate TTX-S VGSCs, but is more potent on insect VGSCs.

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