Solution structure of hpTX2, a toxin from Heteropoda venatoria spider that blocks Kv4.2 potassium channel.
Solution structure of hpTX2, a toxin from Heteropoda venatoria spider that blocks Kv4.2 potassium channel.
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DOI：
10.2210/pdb1emx/pdb
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发表时间：
2001-01
期刊：
影响因子：
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通讯作者：
Cédric Bernard;Christian Legros;G. Ferrat;Ulrike Bischoff;Annette Marquardt;Olaf Pongs;Hervé Darbon
中科院分区：
文献类型：
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作者：
Cédric Bernard;Christian Legros;G. Ferrat;Ulrike Bischoff;Annette Marquardt;Olaf Pongs;Hervé Darbon
HpTX2是毒蜘蛛毒液中的一种毒素，已被证明与Kv4.2钾通道结合。我们用常规的二维核磁共振技术结合距离几何和分子动力学确定了重组HpTX2的溶液结构。计算的结构属于抑制性Cystin结结构家族，该家族存在一个紧凑的二硫键核心，从中出现四个环。检测到定义不佳的双链反平行β-折叠(残基20-23和25-28)。通过对静电电荷各向异性的分析，我们提出了一个HpTX2的功能图谱，该图谱不同于Kappa-conotoxxPVIIA所描述的功能图谱，而与轮藻毒素的功能图谱有很强的相关性。HpTX2的偶极矩方向通过K27出现，因此K27可能是关键的赖氨酸残基。紧邻该赖氨酸的是第二碱性残基R23、芳香族簇(F7、W25、W30)和疏水侧链(L24)。推测功能表面芳香族侧链的高密度以及天冬酰胺的缺乏被认为是HpTX2对Kv4.2通道的特异性的结构基础。
HpTX2 is a toxin from the venom of Heteropoda venatoria spider that has been demonstrated to bind on Kv4.2 potassium channel. We have determined the solution structure of recombinant HpTX2 by use of conventional two-dimensional NMR techniques followed by distance-geometry and molecular dynamics. The calculated structure belongs to the Inhibitory Cystin Knot structural family that consists in a compact disulfide-bonded core, from which four loops emerge. A poorly defined two-stranded antiparallel beta-sheet (residues 20-23 and 25-28) is detected. Analysis of the electrostatic charge anisotropy allows us to propose a functional map of HpTX2 different from the one described for kappa-conotoxin PVIIA, but strongly related to the one of charybdotoxin. The orientation of the dipole moment of HpTX2 emerges through K27 which could therefore be the critical lysine residue. Close to this lysine are a second basic residue, R23, an aromatic cluster (F7, W25, W30) and an hydrophobic side chain (L24). The high density in aromatic side chains of the putative functional surface as well as the lack of an asparagine is proposed to be the structural basis of the specificity of HpTX2 toward Kv4.2 channel.