Tightening of the ATP-binding sites induces the opening of P2X receptor channels
Tightening of the ATP-binding sites induces the opening of P2X receptor channels
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DOI：
10.1038/emboj.2012.75
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发表时间：
2012-05-02
期刊：
影响因子：
11.4
通讯作者：
Grutter, Thomas
中科院分区：
文献类型：
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作者：
Jiang, Ruotian;Taly, Antoine;Grutter, Thomas
配体门控离子通道响应激动剂结合的开放是生物学中的基本过程。在ATP门控P2 X受体中，对ATP结合与通道开放的分子事件知之甚少。在本文中，我们确定的ATP位点的结构变化，伴随着P2 X2受体激活工程细胞外锌桥在假定的移动的地区，揭示了正常模式分析。我们提供的证据表明，收紧的ATP网站形状像开放的“下巴”诱导开放的P2 X离子通道。我们发现，ATP结合有利于下巴收紧，而竞争性拮抗剂的结合，防止门控诱导的这种运动。我们的数据揭示了结合颚的内在动力学，并为P2 X受体激活机制提供了新的结构见解。The EMBO Journal（2012）31，2134-2143. doi：10.1038/daj.2012.75; 2012年3月30日在线发布
The opening of ligand-gated ion channels in response to agonist binding is a fundamental process in biology. In ATP-gated P2X receptors, little is known about the molecular events that couple ATP binding to channel opening. In this paper, we identify structural changes of the ATP site accompanying the P2X2 receptor activation by engineering extracellular zinc bridges at putative mobile regions as revealed by normal mode analysis. We provide evidence that tightening of the ATP sites shaped like open 'jaws' induces opening of the P2X ion channel. We show that ATP binding favours jaw tightening, whereas binding of a competitive antagonist prevents gating induced by this movement. Our data reveal the inherent dynamic of the binding jaw, and provide new structural insights into the mechanism of P2X receptor activation. The EMBO Journal (2012) 31, 2134-2143. doi:10.1038/emboj.2012.75; Published online 30 March 2012