Function and solution structure of hainantoxin‐I, a novel insect sodium channel inhibitor from the Chinese bird spider Selenocosmia hainana1

FEBS Letters

Xie, Jinyun³  Bosmans, Frank²  Li, Dongling¹  Hu, Weijun³  Liang, Songping³  Tytgat, Jan²  Xiao, Yucheng³ 

[1] College of Life Sciences, Peking University, Beijing 100871, PR China;Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, 3000 Leuven, Belgium;College of Life Sciences, Hunan Normal University, Changsha 410081, PR China

关键词: Hainantoxin-i;    Neurotoxin;    Sodium channel;    Solution structure;    ICK motif;    HNTX-I;    hainantoxin-I;    VGSC;    voltage-gated sodium channel;    TTX;    tetrodotoxin;    ICK;    inhibitor cystine knot;    RP-HPLC;    reversed-phase high performance liquid chromatography;    MALDI-TOF;    matrix-assisted laser desorption/ionization time-of-flight;    TCEP;    Tris (2-carboxyethyl)phosphine;    NOE;    nuclear Overhauser effect spectroscopy;   

DOI  :  10.1016/S0014-5793(03)01303-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Hainantoxin-I is a novel peptide toxin, purified from the venom of the Chinese bird spider Selenocosmia hainana (=Ornithoctonus hainana). It includes 33 amino acid residues with a disulfide linkage of I–IV, II–V and III–VI, assigned by partial reduction and sequence analysis. Under two-electrode voltage-clamp conditions, hainantoxin-I can block rNa_v1.2/β₁ and the insect sodium channel para/tipE expressed in Xenopus laevis oocytes with IC₅₀ values of 68±6 μM and 4.3±0.3 μM respectively. The three-dimensional solution structure of hainantoxin-I belongs to the inhibitor cystine knot structural family determined by two-dimensional ¹H nuclear magnetic resonance techniques. Structural comparison of hainantoxin-I with those of other toxins suggests that the combination of the charged residues and a vicinal hydrophobic patch should be responsible for ligand binding. This is the first report of an insect sodium channel blocker from spider venom and it provides useful information for the structure–function relationship studies of insect sodium channels.

【 授权许可】

Unknown