The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity.
The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity.
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DOI：
10.1038/nsmb.1738
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发表时间：
2010-01
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
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在电压门控钠、钾和钙通道中，离子传导和电压感应的功能是由两个不同的结构单元完成的：孔域和电压感应域（VSD）。在Hv1电压门控质子通道中，VSD具有两种功能的显著特性。最近发现Hv1具有二聚性，并形成由两个孔组成的通道。然而，当二聚化被阻止时，这些通道也会起作用，这就提出了一个关于二聚化功能作用的问题。在这里，我们发现Hv1二聚体的两个亚基在门控过程中相互影响，具有正的协同性，形成了两个孔对电压的响应。我们还发现两个电压传感器在开孔之前会发生构象变化，并且这些构象变化在两个亚基之间是变构耦合的。我们的结果指出了二聚化在调节Hv1活性中的主要作用。
In voltage-gated sodium, potassium, and calcium channels the functions of ion conduction and voltage sensing are performed by two distinct structural units: the pore domain and the voltage-sensing domain (VSD). In the Hv1 voltage-gated proton channel, the VSD has the remarkable property of performing both functions. Hv1 was recently found to dimerize and to form channels made of two pores. However, the channels were also found to function when dimerization was prevented, raising a question about the functional role of dimerization. Here we show that the two subunits of the Hv1 dimer influence one another during gating, with positive cooperativity shaping the response to voltage of the two pores. We also find that the two voltage sensors undergo conformational changes that precede pore opening and that these conformational changes are allosterically coupled between the two subunits. Our results point to a major role of dimerization in the modulation of Hv1 activity.
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影响因子：
16.2
作者：
Aggarwal, SK;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
16.2
作者：
Larsson, HP;Baker, OS;Isacoff, EY
通讯作者：
Isacoff, EY
影响因子：
3.8
作者：
Ledwell, JL;Aldrich, RW
通讯作者：
Aldrich, RW
DOI：
10.1073/pnas.0902761106
发表时间：
2009-05-05
影响因子：
11.1
作者：
Ramsey, I. Scott;Ruchti, Evelyne;Clapham, David E.
通讯作者：
Clapham, David E.
DOI：
10.1152/ajprenal.1997.273.4.f516
发表时间：
1997-10-01
影响因子：
4.2
作者：
Choe, H;Zhou, H;Sackin, H
通讯作者：
Sackin, H