Structural Insights into Divalent Cation Modulations of ATP-Gated P2X Receptor Channels
Structural Insights into Divalent Cation Modulations of ATP-Gated P2X Receptor Channels
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DOI：
10.1016/j.celrep.2015.12.087
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发表时间：
2016-02-02
期刊：
影响因子：
8.8
通讯作者：
Nureki, Osamu
中科院分区：
文献类型：
--
作者：
Kasuya, Go;Fujiwara, Yuichiro;Nureki, Osamu
P2X受体是一种三聚体ATP门控阳离子通道，广泛参与从神经传递到疼痛和味觉信号转导等多种生理过程。通道门控的调节，包括二价阳离子的调节，促成了P2X受体的这些不同的生理功能。在这里，我们报道了在ATP和锌离子存在的情况下，来自墨西哥湾沿岸斑点钝隔茧蜂的无脊椎动物P2X受体的晶体结构，以及电生理和计算分析。该结构在胞外区显示了两个不同的金属结合部位，M1和M2。M1位点位于三聚体界面，通过促进胞外结构域的结构变化来促进锌离子的增强。相反，M2位点与ATP结合位点可能有助于镁离子的调节。总体而言，我们的工作为P2X受体的二价阳离子调节提供了结构上的见解。
P2X receptors are trimeric ATP-gated cation channels involved in physiological processes ranging widely from neurotransmission to pain and taste signal transduction. The modulation of the channel gating, including that bydivalent cations, contributes to these diverse physiological functions of P2X receptors. Here, we report the crystal structure of an invertebrate P2X receptor from the Gulf Coast tick Amblyomma maculatum in the presence of ATP and Zn2+ ion, together with electrophysiological and computational analyses. The structure revealed two distinct metal binding sites, M1 and M2, in the extracellular region. The M1 site, located at the trimer interface, is responsible for Zn2+ potentiation by facilitating the structural change of the extracellular domain for pore opening. In contrast, the M2 site, coupled with the ATP binding site, might contribute to regulation by Mg2+. Overall, our work provides structural insights into the divalent cation modulations of P2X receptors.