A Novel Voltage Sensor in the Orthosteric Binding Site of the M2 Muscarinic Receptor
A Novel Voltage Sensor in the Orthosteric Binding Site of the M2 Muscarinic Receptor
复制标题
DOI：
10.1016/j.bpj.2016.08.035
复制
发表时间：
2016-10-04
影响因子：
3.4
通讯作者：
Ben-Chaim, Yair
中科院分区：
文献类型：
--
作者：
Barchad-Avitzur, Ofra;Priest, Michael F.;Ben-Chaim, Yair
G 蛋白偶联受体 (GPCR) 介导体内许多信号转导过程。这些受体对电压敏感的发现改变了我们对其行为的理解。 M2 毒蕈碱乙酰胆碱受体 (M2R) 被发现表现出去极化诱导的电荷运动相关电流，这意味着这种原型 GPCR 具有电压传感器。然而，GPCR 中不存在在电压门控通道中充当电压传感器的典型域，这使得在后者中寻找电压传感器具有挑战性。在这里，我们检查了 M2R 并描述了一种由酪氨酸残基组成的电压传感器。该电压传感器对于激动剂与受体结合的电压依赖性至关重要。这里发现的基于酪氨酸的电压传感器构成了膜蛋白可以感知电压的非规范传感器。
G protein-coupled receptors (GPCRs) mediate many signal transduction processes in the body. The discovery that these receptors are voltage-sensitive has changed our understanding of their behavior. The M2 muscarinic acetylcholine receptor (M2R) was found to exhibit depolarization-induced charge movement-associated currents, implying that this prototypical GPCR possesses a voltage sensor. However, the typical domain that serves as a voltage sensor in voltage-gated channels is not present in GPCRs, making the search for the voltage sensor in the latter challenging. Here, we examine the M2R and describe a voltage sensor that is comprised of tyrosine residues. This voltage sensor is crucial for the voltage dependence of agonist binding to the receptor. The tyrosine-based voltage sensor discovered here constitutes a noncanonical by which membrane proteins may sense voltage.