Gating the pore of P2X receptor channels
Gating the pore of P2X receptor channels
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DOI：
10.1038/nn.2151
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发表时间：
2008-08-01
影响因子：
25
通讯作者：
Swartz, Kenton J.
中科院分区：
文献类型：
--
作者：
Li, Mufeng;Chang, Tsg-Hui;Swartz, Kenton J.
哺乳动物中三个配体激活离子通道家族介导可兴奋细胞之间的突触通讯。对于烟碱乙酰胆碱受体相关的五聚体通道和谷氨酸受体等四聚体通道，其成孔区和门区已被广泛研究。相比之下，三聚体P2X受体通道的结构知之甚少，这是一个由ATP激活的通道家族，在神经元信号传导、疼痛传递和炎症中很重要。为了确定P2X受体通道的孔形成和门区，我们在两个跨膜（TM）片段中引入了半胱氨酸残基，并研究了它们对硫醇反应性化合物和离子的可及性。我们的研究结果表明，TM2排列在中心离子传导孔上，TM1位于TM2的外围，在封闭状态下，由TM2外部区域形成的栅极使离子流动最小化。
Three families of ligand-activated ion channels mediate synaptic communication between excitable cells in mammals. For pentameric channels related to nicotinic acetylcholine receptors and tetrameric channels such as glutamate receptors, the pore-forming and gate regions have been studied extensively. In contrast, little is known about the structure of trimeric P2X receptor channels, a family of channels that are activated by ATP and are important in neuronal signaling, pain transmission and inflammation. To identify the pore-forming and gate regions in P2X receptor channels, we introduced cysteine residues throughout the two transmembrane (TM) segments and studied their accessibility to thiol-reactive compounds and ions. Our results show that TM2 lines the central ion-conduction pore, TM1 is positioned peripheral to TM2 and the flow of ions is minimized in the closed state by a gate formed by the external region of TM2.