PIP₂-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6.
PIP₂-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6.
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由于 S4-S5 和 S6 之间的相互作用减弱，PIP2 依赖性耦合在 Kv7.1 中很突出
DOI：
10.1038/srep07474
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发表时间：
2015-01-06
影响因子：
4.6
通讯作者：
Tarek M
中科院分区：
文献类型：
--
作者：
Kasimova MA;Zaydman MA;Cui J;Tarek M
电压门控钾（Kv）通道功能的关键方面之一是其两个组成域，电压传感器（VSD）和孔之间的有效通信。这种被称为偶联的通信可能通过这些结构域之间的相互作用直接传递，并且如最近提出的那样，通过与磷脂酰肌醇-4,5-二磷酸（PIP2）的相互作用间接传递，PIP2是内质膜小叶的一种次要脂质。在这里，我们展示了由蛋白质-蛋白质或蛋白质-脂质相互作用介导的耦合的两个组成部分如何在Kv7.1功能中发挥作用。一方面，通过分子动力学模拟，我们确定了一个Kv7.1 pip2结合位点，该位点涉及在pip2依赖性偶联中发挥关键作用的残基。另一方面，理论和实验相结合的方法表明，静电斥力削弱了VSD （S4-S5）段与孔（S6）之间的直接相互作用。最后，我们得出结论，由于蛋白质相互作用减弱，pip2依赖性偶联在Kv7.1中尤为突出。
Among critical aspects of voltage-gated potassium (Kv) channels' functioning is the effective communication between their two composing domains, the voltage sensor (VSD) and the pore. This communication, called coupling, might be transmitted directly through interactions between these domains and, as recently proposed, indirectly through interactions with phosphatidylinositol-4,5-bisphosphate (PIP2), a minor lipid of the inner plasma membrane leaflet. Here, we show how the two components of coupling, mediated by protein-protein or protein-lipid interactions, both contribute in the Kv7.1 functioning. On the one hand, using molecular dynamics simulations, we identified a Kv7.1 PIP2binding site that involves residues playing a key role in PIP2-dependent coupling. On the other hand, combined theoretical and experimental approaches have shown that the direct interaction between the segments of the VSD (S4–S5) and the pore (S6) is weakened by electrostatic repulsion. Finally, we conclude that due to weakened protein-protein interactions, the PIP2-dependent coupling is especially prominent in Kv7.1.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
4.8
作者：
Abderemane-Ali, Fayal;Es-Salah-Lamoureux, Zeineb;Loussouarn, Gildas
通讯作者：
Loussouarn, Gildas
DOI：
10.1085/jgp.201010573
发表时间：
2011-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Haddad GA;Blunck R
通讯作者：
Blunck R
DOI：
10.1085/jgp.200810048
发表时间：
2008-12
期刊：
The Journal of general physiology
影响因子：
--
作者：
Labro AJ;Raes AL;Grottesi A;Van Hoorick D;Sansom MS;Snyders DJ
通讯作者：
Snyders DJ
影响因子：
3.8
作者：
Hackos, David H;Chang, Tsg-Hui;Swartz, Kenton J
通讯作者：
Swartz, Kenton J