Movement of 'gating charge' is coupled to ligand binding in a G-protein-coupled receptor
Movement of 'gating charge' is coupled to ligand binding in a G-protein-coupled receptor
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DOI：
10.1038/nature05259
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发表时间：
2006-11-02
期刊：
影响因子：
64.8
通讯作者：
Parnas, Hanna
中科院分区：
文献类型：
--
作者：
Ben-Chaim, Yair;Chanda, Baron;Parnas, Hanna
g蛋白偶联受体（gpcr）的激动剂结合激活控制着大多数信号转导过程(1)。虽然这些受体跨越细胞膜，但它们不被认为是电压敏感的。最近有研究表明，GPCRs的活性（2-5）及其对激动剂的亲和力(6)都受膜电位的调节。然而，目前尚不清楚gpcr是否内在地响应膜电位的变化。在这里，我们展示了两个原型gpcr， m2和m1毒蕈碱受体（m2R和m1R），显示电荷运动相关的电流，类似于电压门控通道的“门控电流”。m2R的门控电荷-电压关系与受体对乙酰胆碱亲和力的电压依赖性密切相关。将m2R和m1R与它们的G蛋白偶联的环在将电压感应偶联到激动剂结合亲和力方面具有关键作用。我们的数据强烈表明，gpcr可以作为跨膜电位和外部化学信号的传感器。
Activation by agonist binding of G-protein-coupled receptors (GPCRs) controls most signal transduction processes(1). Although these receptors span the cell membrane, they are not considered to be voltage sensitive. Recently it was shown that both the activity of GPCRs(2-5) and their affinity towards agonists(6) are regulated by membrane potential. However, it remains unclear whether GPCRs intrinsically respond to changes in membrane potential. Here we show that two prototypical GPCRs, the m2 and m1 muscarinic receptors (m2R and m1R), display charge-movement-associated currents analogous to 'gating currents' of voltage-gated channels. The gating charge - voltage relationship of m2R correlates well with the voltage dependence of the affinity of the receptor for acetylcholine. The loop that couples m2R and m1R to their G protein has a crucial function in coupling voltage sensing to agonist-binding affinity. Our data strongly indicate that GPCRs serve as sensors for both transmembrane potential and external chemical signals.