Sequential formation of ion pairs during activation of a sodium channel voltage sensor
Sequential formation of ion pairs during activation of a sodium channel voltage sensor
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DOI：
10.1073/pnas.0912307106
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发表时间：
2009-12-29
影响因子：
11.1
通讯作者：
Catterall, William A.
中科院分区：
文献类型：
--
作者：
DeCaen, Paul G.;Yarov-Yarovoy, Vladimir;Catterall, William A.
生物学中的电信号依赖于由电压门控离子通道S4段介导的独特机电转导过程。这些跨膜片段在电场的作用下被称为“门控电荷”的带正电荷的氨基酸残基向外驱动，这些氨基酸残基位于S4跨膜片段的三个残基间隔上，这种运动与孔的打开有关。在这里，我们使用二硫锁方法来证明在激活过程中，S4段的第四个门控电荷（R4）和S2段的两个酸性残基之间形成了顺序的离子对。R4首先在S2片段的胞内末端与E70相互作用，然后在胞外末端与D60相互作用。Rosetta膜方法分析揭示了门控孔的三维结构，因为这些离子对依次形成，催化了电压依赖性激活所需的S4跨膜运动。我们的结果直接证明了顺序离子对形成是电压传感器功能的滑动螺旋模型的基本特征，但与其他广泛讨论的门控模型不兼容。
Electrical signaling in biology depends upon a unique electromechanical transduction process mediated by the S4 segments of voltage-gated ion channels. These transmembrane segments are driven outward by the force of the electric field on positively charged amino acid residues termed "gating charges," which are positioned at three-residue intervals in the S4 transmembrane segment, and this movement is coupled to opening of the pore. Here, we use the disulfide-locking method to demonstrate sequential ion pair formation between the fourth gating charge in the S4 segment (R4) and two acidic residues in the S2 segment during activation. R4 interacts first with E70 at the intracellular end of the S2 segment and then with D60 near the extracellular end. Analysis with the Rosetta Membrane method reveals the 3-D structures of the gating pore as these ion pairs are formed sequentially to catalyze the S4 transmembrane movement required for voltage-dependent activation. Our results directly demonstrate sequential ion pair formation that is an essential feature of the sliding helix model of voltage sensor function but is not compatible with the other widely discussed gating models.