Molecular determinants of coupling between the domain III voltage sensor and pore of a sodium channel.
Molecular determinants of coupling between the domain III voltage sensor and pore of a sodium channel.
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DOI：
10.1038/nsmb.1749
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发表时间：
2010-02
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
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在电压依赖的钠通道中，电压传感器在去极化时的激活导致孔门打开。为了阐明这种构象耦合的原理，我们使用电压箝位荧光法和色氨酸扫描诱变法研究了钠离子通道III区域的一个假定的门控界面。大多数突变对电压传感器的激活和孔隙打开具有类似的能量效应。然而，几个突变稳定了激活的电压传感器，同时破坏了开放孔的稳定。将这些突变映射到钠通道的同源模型上表明，大多数突变定位于门控界面的铰链区域。我们的分析表明，当电压传感器和孔处于静止或激活构象时，这些残留物参与了电压传感器和孔的能量耦合，这支持了电压依赖离子通道中的机电耦合涉及由弹性铰链连接的刚性段的运动的概念。
In a voltage-dependent sodium channel, the activation of voltage-sensors upon depolarization leads to the opening of pore gates. To elucidate the principles underlying this conformational coupling, we investigated a putative gating interface in domain III of the sodium channel using voltage-clamp fluorimetry and tryptophan-scanning mutagenesis. Most mutations have similar energetic effects on voltage-sensor activation and pore opening. However, several mutations stabilized the activated voltage-sensor while concurrently destabilizing the open pore. Mapping of these mutations onto a homology model of the sodium channel showed that most localize to hinge regions of the gating interface. Our analysis shows that these residues are involved in energetic coupling of the voltage-sensor and the pore when both are in the resting or activated conformations, supporting the notion that electromechanical coupling in a voltage-dependent ion channel involves the movement of rigid segments connected by elastic hinges.
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影响因子：
64.8
作者：
Long, Stephen B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
3.8
作者：
Holmgren, M;Smith, PL;Yellen, G
通讯作者：
Yellen, G
影响因子：
3.8
作者：
Ledwell, JL;Aldrich, RW
通讯作者：
Aldrich, RW
电压传感器和孔之间需要两个独立的接口来实现电压依赖性 K(+) 通道的功能。
影响因子：
9.8
作者：
Lee, Seok-Yong;Banerjee, Anirban;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick