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8.B.3 The Huwentoxin-1 (Huwentoxin-1) Family

Huwentoxin-1 is an 81 aa neurotoxin precursor that is a Ca2+ channel inhibitor (Diao et al., 2003). Huwentoxin-1 is a lethal neurotoxin that binds to the nicotinic acetylcholine receptor and blocks neuromuscular transmission. It possesses presynaptic activity that affects the release of neurotransmitters from autonomic nerve endings of both cholinergic and adrenergic neuroeffector junctions. It selectively inhibits N-type calcium channels and has only very weak effects on L-type calcium channel.

Hainantoxin-4 from the Chinese bird spider, Selenocosmia (Ornithoctonus) hainana, is a 35 aa processed peptide neurotoxin. It selectively blocks neuronal tetrodotoxin-sensitive voltage-gated Na+ channels as a monomer (Liu et al., 2002; Xu et al., 2005). Structures of hainantoxins have been determined by NMR (Li et al., 2004; Qu et al., 1997). These mature toxins each have a disulfide bridge and are amidated at their C-termini. Huwentoxin-IV is an inhibitor cystine knot peptide from Chinese tarantula Ornithoctonus huwena venom that blocks tetrodotoxin-sensitive voltage-gated sodium channels from mammalian sensory neurons (Xiao et al., 2008). The solution structure has been solved (Peng et al., 2002).


This family belongs to the: Huwentoxin Superfamily.

References associated with 8.B.3 family:

Diao, J., Lin, Y., Tang, J., and Liang, S. (2003). cDNA sequence analysis of seven peptide toxins from the spider Selenocosmia huwena. Toxicon 42: 715-723. 14757201
Li, D., Xiao, Y., Xu, X., Xiong, X., Lu, S., Liu, Z., Zhu, Q., Wang, M., Gu, X., and Liang, S. (2004). Structure-activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers. J. Biol. Chem. 279: 37734-37740. 15201273
Liu, Z.H., Chen, P., and Liang, S.P. (2002). Synthesis and oxidative refolding of hainantoxin-IV. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 34: 516-519. 12098779
Ono, S., T. Kimura, and T. Kubo. (2011). Characterization of voltage-dependent calcium channel blocking peptides from the venom of the tarantula Grammostola rosea. Toxicon 58: 265-276. 21740921
Peng, K., Q. Shu, Z. Liu, and S. Liang. (2002). Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena. J. Biol. Chem. 277: 47564-47571. 12228241
Qu, Y., Liang, S., Ding, J., Liu, X., Zhang, R., and Gu, X. (1997). Proton nuclear magnetic resonance studies on huwentoxin-I from the venom of the spider Selenocosmia huwena: 2. Three-dimensional structure in solution. J. Protein Chem. 16: 565-574. 9263120
Tang, C., X. Zhou, P.T. Nguyen, Y. Zhang, Z. Hu, C. Zhang, V. Yarov-Yarovoy, P.G. DeCaen, S. Liang, and Z. Liu. (2017). A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel. FASEB J. [Epub: Ahead of Print] 28400471
Tao, H., J.J. Chen, Y.C. Xiao, Y.Y. Wu, H.B. Su, D. Li, H.Y. Wang, M.C. Deng, M.C. Wang, Z.H. Liu, and S.P. Liang. (2013). Analysis of the interaction of tarantula toxin Jingzhaotoxin-III (β-TRTX-Cj1α) with the voltage sensor of Kv2.1 uncovers the molecular basis for cross-activities on Kv2.1 and Nav1.5 channels. Biochemistry 52: 7439-7448. 24044413
Tao, H., Y. Wu, M. Deng, J. He, M. Wang, Y. Xiao, and S. Liang. (2013). Molecular determinants for the tarantula toxin jingzhaotoxin-I interacting with potassium channel Kv2.1. Toxicon 63: 129-136. 23246579
Xiao, Y., X. Luo, F. Kuang, M. Deng, M. Wang, X. Zeng, and S. Liang. (2008). Synthesis and characterization of huwentoxin-IV, a neurotoxin inhibiting central neuronal sodium channels. Toxicon. 51: 230-239. 18054060
Xu, X., Xiong, X., Li, D.L., Xiao, Y.C., Wang, X.C., and Liang, S.P. (2005). Solid-phase synthesis and biological characterization of S12A-HNTX-IV and R29A-HNTX-IV: two mutants of hainantoxin-IV. Sheng Wu Gong Cheng Xue Bao 21: 92-96 (Chinese). 15859335