Structure of the Acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1
Structure of the Acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1
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DOI：
10.1038/ncomms1917
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发表时间：
2012-07-01
影响因子：
16.6
通讯作者：
Ruf, Armin
中科院分区：
文献类型：
--
作者：
Dawson, Roger J. P.;Benz, Joerg;Ruf, Armin
毒液来源的肽毒素可以改变神经元兴奋通道的门控特性。它们如何结合并干扰离子的流动而不直接阻断离子渗透途径仍然是难以捉摸的。本文报道了三聚体鸡酸敏感离子通道1与高选择性门控调节剂Psalmotoxin 1配合物在3.0埃分辨率下的晶体结构。该结构揭示了三种毒素分子在酸感离子通道1的质子敏感酸性口袋结合的分子相互作用，以及与离子通道上方中央前庭捕获的阳离子一致的电子密度。疏水贴片和基本簇是Psalmotoxin 1结合的关键结构元件，将两个独立的调控区域锁定在它们相对脱敏的类似排列中。我们的研究结果提供了门控调节剂毒素结合的一般概念，表明这两个表面基元都需要改变离子通道的门控特性。
Venom-derived peptide toxins can modify the gating characteristics of excitatory channels in neurons. How they bind and interfere with the flow of ions without directly blocking the ion permeation pathway remains elusive. Here we report the crystal structure of the trimeric chicken Acid-sensing ion channel 1 in complex with the highly selective gating modifier Psalmotoxin 1 at 3.0 angstrom resolution. The structure reveals the molecular interactions of three toxin molecules binding at the proton-sensitive acidic pockets of Acid-sensing ion channel 1 and electron density consistent with a cation trapped in the central vestibule above the ion pathway. A hydrophobic patch and a basic cluster are the key structural elements of Psalmotoxin 1 binding, locking two separate regulatory regions in their relative, desensitized-like arrangement. Our results provide a general concept for gating modifier toxin binding suggesting that both surface motifs are required to modify the gating characteristics of an ion channel.