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Small vertical movement of a K+ channel voltage sensor measured with luminescence energy transfer

机译：用发光能量转移测量的K +通道电压传感器的垂直运动很小

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Voltage-gated ion channels open and close in response to voltage changes across electrically excitable cell membranes(1). Voltage-gated potassium (Kv) channels are homotetramers with each subunit constructed from six transmembrane segments, S1 - S6 (ref. 2). The voltage-sensing domain ( segments S1 - S4) contains charged arginine residues on S4 that move across the membrane electric field(2,3), modulating channel open probability. Understanding the physical movements of this voltage sensor is of fundamental importance and is the subject of controversy. Recently, the crystal structure of the KvAP(4) channel motivated an unconventional 'paddle model' of S4 charge movement, indicating that the segments S3b and S4 might move as a unit through the lipid bilayer with a large ( 15-20-angstrom) transmembrane displacement(5). Here we show that the voltage-sensor segments do not undergo significant transmembrane translation. We tested the movement of these segments in functional Shaker K 1 channels by using luminescence resonance energy transfer to measure distances between the voltage sensors and a pore-bound scorpion toxin. Our results are consistent with a 2-angstrom vertical displacement of S4, not the large excursion predicted by the paddle model. This small movement supports an alternative model in which the protein shapes the electric field profile, focusing it across a narrow region of S4 ( ref. 6).
机译：电压门控离子通道响应于可电激发细胞膜上的电压变化而打开和关闭（1）。电压门控钾（Kv）通道是同四聚体，每个亚基由六个跨膜片段S1-S6（参考文献2）构成。电压感测域（段S1-S4）包含S4上带电的精氨酸残基，它们在膜电场上移动（2,3），从而调节通道打开的可能性。了解此电压传感器的物理运动至关重要，并且是有争议的主题。最近，KvAP（4）通道的晶体结构激发了S4电荷运动的非常规“桨状模型”，这表明段S3b和S4可能会作为一个单元移动通过大的脂质双层（15-20埃）跨膜置换（5）。在这里，我们显示电压传感器段没有经历明显的跨膜转换。我们通过使用发光共振能量转移来测量电压传感器和结合有孔的蝎子毒素之间的距离，从而测试了这些振荡器在功能性Shaker K 1通道中的运动。我们的结果与S4的2埃垂直位移一致，而不是桨模型预测的大偏移。这种小的运动支持了一种替代模型，其中蛋白质形成电场轮廓，将其聚焦在S4的狭窄区域上（参考文献6）。

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