Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains.
Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains.
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DOI：
10.1016/j.neuron.2012.11.013
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发表时间：
2013-01-23
期刊：
影响因子：
16.2
通讯作者：
Tombola F
中科院分区：
文献类型：
--
作者：
Hong L;Pathak MM;Kim IH;Ta D;Tombola F
电压门控钠、钾和钙通道由四个电压敏感结构域（VSD）控制的孔结构域（PD）组成。PD包含离子渗透途径和位于膜的细胞内侧的激活门。已知大量小分子通过充当开放通道阻断剂来抑制PD。电压门控质子通道Hv1由两个VSD组成，缺乏PD。室间隔缺损中激活门的位置未知，室间隔缺损的开放通道阻滞剂尚未确定。在这里，我们描述了一类小分子作为开放通道阻滞剂的Hv1室间隔缺损，并发现，一个高度保守的苯丙氨酸的电荷转移中心的室间隔缺损中起着关键作用，在阻滞剂结合。然后，我们使用的阻断剂之一，表明Hv1包含两个细胞内和变构耦合门。
Voltage-gated sodium, potassium, and calcium channels are made of a pore domain (PD) controlled by four voltage-sensing domains (VSDs). The PD contains the ion permeation pathway and the activation gate located on the intracellular side of the membrane. A large number of small molecules are known to inhibit the PD by acting as open channel blockers. The voltage-gated proton channel Hv1 is made of two VSDs and lacks the PD. The location of the activation gate in the VSD is unknown and open channel blockers for VSDs have not yet been identified. Here we describe a class of small molecules which act as open channel blockers on the Hv1 VSD and find that a highly conserved phenylalanine in the charge transfer center of the VSD plays a key role in blocker binding. We then use one of the blockers to show that Hv1 contains two intracellular and allosterically-coupled gates.
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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：
5.6
作者：
Lee, Seok-Yong;Letts, James A.;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
3.8
作者：
Holmgren, M;Smith, PL;Yellen, G
通讯作者：
Yellen, G
DOI：
10.1085/jgp.58.4.413
发表时间：
1971-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Armstrong CM
通讯作者：
Armstrong CM
DOI：
10.1073/pnas.1103397108
发表时间：
2011-04-19
影响因子：
11.1
作者：
Lacroix, Jerome J.;Bezanilla, Francisco
通讯作者：
Bezanilla, Francisco