Voltage sensor-trapping:: Enhanced activation of sodium channels by β-scorpion toxin bound to the S3-S4 loop in domain II
Voltage sensor-trapping:: Enhanced activation of sodium channels by β-scorpion toxin bound to the S3-S4 loop in domain II
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DOI：
10.1016/s0896-6273(00)80606-6
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发表时间：
1998-10-01
期刊：
影响因子：
16.2
通讯作者：
Catterall, WA
中科院分区：
文献类型：
--
作者：
Cestèle, S;Qu, YS;Catterall, WA
多肽神经毒素通过与细胞外受体位点结合来改变离子通道的门控，即便电压传感器位于其S4跨膜区段。通过对钠通道嵌合体的分析，在此表明一种β -蝎毒素通过与一个受体位点结合，使激活的电压依赖性负向偏移，并增强关闭状态下的失活，该受体位点需要α亚基第II结构域中S4区段细胞外端的S3 - S4环中的甘氨酸845（Gly - 845）。毒素作用需要预先去极化以驱使S4电压传感器向外移动，但这些效应在突变体G845N中丧失。结果揭示了一种毒素作用的电压传感器捕获模型，其中II S4电压传感器因毒素结合而被捕获在其向外的激活位置。
Polypeptide neurotoxins alter ion channel gating by binding to extracellular receptor sites, even though the voltage sensors are in their S4 transmembrane segments. By analysis of sodium channel chimeras, a beta-scorpion toxin is shown here to negatively shift voltage dependence of activation and enhance closed state inactivation by binding to a receptor site that requires glycine 845 (Gly-845) in the S3-S4 loop at the extracellular end of the S4 segment in domain II of the alpha subunit. Toxin action requires prior depolarization to drive the S4 voltage sensors outward, but these effects are lost in the mutant G845N. The results reveal a voltage sensor-trapping model of toxin action in which the IlS4 voltage sensor is trapped in its outward, activated position by toxin binding.