The principle of gating charge movement in a voltage-dependent K+ channel

The principle of gating charge movement in a voltage-dependent K+ channel
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DOI:
10.1038/nature01581
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发表时间:
2003-05-01
期刊:
影响因子:
64.8
通讯作者:
MacKinnon, R
MacKinnon, R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Jiang, YX;Ruta, V;MacKinnon, R

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通道开放对膜电压的陡峭依赖性使得电压依赖性K+通道几乎像开关一样打开。开放是由门控电荷的运动驱动的,门控电荷来源于蛋白质螺旋S4片段上的精氨酸残基。每个S4段在通道的外周上形成一半的“电压传感器桨”。在这里,我们表明,电压传感器桨位于膜内,靠近细胞内表面,当通道关闭时,和桨移动一个很大的距离跨膜从内到外时,通道打开。KvAP通道重建成平面脂质膜,并研究使用单克隆Fab片段,电压传感器毒素,亲和素结合栓系生物素。我们的研究结果使我们得出结论,电压传感器桨的操作有点像连接到杠杆的疏水阳离子,使膜电场打开和关闭孔。
The steep dependence of channel opening on membrane voltage allows voltage-dependent K+ channels to turn on almost like a switch. Opening is driven by the movement of gating charges that originate from arginine residues on helical S4 segments of the protein. Each S4 segment forms half of a 'voltage-sensor paddle' on the channel's outer perimeter. Here we show that the voltage-sensor paddles are positioned inside the membrane, near the intracellular surface, when the channel is closed, and that the paddles move a large distance across the membrane from inside to outside when the channel opens. KvAP channels were reconstituted into planar lipid membranes and studied using monoclonal Fab fragments, a voltage-sensor toxin, and avidin binding to tethered biotin. Our findings lead us to conclude that the voltage-sensor paddles operate somewhat like hydrophobic cations attached to levers, enabling the membrane electric field to open and close the pore.