Relative motions between left flipper and dorsal fin domains favour P2X4 receptor activation
Relative motions between left flipper and dorsal fin domains favour P2X4 receptor activation
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左鳍和背鳍结构域之间的相对运动有利于 P2X4 受体激活
DOI：
10.1038/ncomms5189
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发表时间：
2014-06-01
影响因子：
16.6
通讯作者：
Yu, Ye
中科院分区：
文献类型：
--
作者：
Zhao, Wen-Shan;Wang, Jin;Yu, Ye
通道门控是P2X受体生理功能的基本过程。在这里，我们确定了协调变构的变化，在左鳍（LF）和背鳍（DF）域耦合ATP结合通道门控。LF和DF结构域之间的工程化二硫键交联或锌桥限制了它们的相对运动，显著影响了P2X4受体的通道门控，证实了这些变构变化的重要作用。ATP结合诱导的I208，L217，V291和K193的脂肪链之间的结构域间疏水相互作用的改变与这些协调的相对运动密切相关。这四个残基上的突变导致P2X4受体的通道激活受损或完全消除。我们的数据表明，ATP结合诱导的改变域间的疏水相互作用和随之而来的协调运动的LF和DF域的变构事件必不可少的通道门控P2X4受体。
Channel gating in response to extracellular ATP is a fundamental process for the physiological functions of P2X receptors. Here we identify coordinated allosteric changes in the left flipper (LF) and dorsal fin (DF) domains that couple ATP-binding to channel gating. Engineered disulphide crosslinking or zinc bridges between the LF and DF domains that constrain their relative motions significantly influence channel gating of P2X4 receptors, confirming the essential role of these allosteric changes. ATP-binding-induced alterations in interdomain hydrophobic interactions among I208, L217, V291 and the aliphatic chain of K193 correlate well with these coordinated relative movements. Mutations on those four residues lead to impaired or fully abolished channel activations of P2X4 receptors. Our data reveal that ATP-binding-induced altered interdomain hydrophobic interactions and the concomitant coordinated motions of LF and DF domains are allosteric events essential for the channel gating of P2X4 receptors.