On the role of the first transmembrane domain in cation permeability and flux of the ATP-gated P2X2 receptor
On the role of the first transmembrane domain in cation permeability and flux of the ATP-gated P2X2 receptor
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DOI：
10.1074/jbc.m708713200
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发表时间：
2008-02-22
影响因子：
4.8
通讯作者：
Egan, Terrance M.
中科院分区：
文献类型：
--
作者：
Samways, Damien S. K.;Migita, Keisuke;Egan, Terrance M.
P2 X受体是在ATP存在下打开的七个配体门控离子通道（P2 X（1）-P2 X（7））的家族。我们用丙氨酸扫描诱变和膜片钳光度法研究了大鼠P2 X（2）受体第一跨膜区在阳离子通透性和通量中的作用。三个丙氨酸取代的突变体没有响应ATP，和19的22个功能性受体类似的野生型受体的总ATP门控电流的分数进行钙或钙相对于铯的渗透性。其余三个突变体表现出适度的钙动力学变化。其中两个发生在不太可能以有意义的方式与渗透阳离子相互作用的位点（Gly（30）和Phe（44））。第三个是保守的酪氨酸（Tyr（43）），其可形成钙的孔间结合位点。数据表明，除了Tyr（43）之外，第一个跨膜结构域对P2 X（2）受体的渗透性质贡献很小。
P2X receptors are a family of seven ligand-gated ion channels (P2X(1)-P2X(7)) that open in the presence of ATP. We used ala-nine-scanning mutagenesis and patch clamp photometry to study the role of the first transmembrane domain of the rat P2X(2) receptor in cation permeability and flux. Three alanine-substituted mutants did not respond to ATP, and 19 of the 22 functional receptors resembled the wild-type receptor with regard to the fraction of the total ATP-gated current carried by calcium or the permeability of calcium relative to cesium. The remaining three mutants showed modest changes in calcium dynamics. Two of these occurred at sites (Gly(30) and Phe(44)) that are unlikely to interact with permeating cations in a meaningful way. The third was a conserved tyrosine (Tyr(43)) that may form an inter-pore binding site for calcium. The data suggest that, with the possible exception of Tyr(43), the first transmembrane domain contributes little to the permeation properties of the P2X(2) receptor.