The pore of voltage-gated potassium ion channels is strained when closed.
The pore of voltage-gated potassium ion channels is strained when closed.
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DOI：
10.1038/ncomms2858
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发表时间：
2013
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
电压门控钾通道在细胞膜中形成钾选择性孔。它们响应于跨膜电位的变化而打开或关闭，并且对于产生动作电位以及因此对于心脏和大脑的功能至关重要。虽然有人提出了关闭这些渠道的机制，但尚不清楚是什么推动了这些渠道的开放。在这里，我们使用自由能分子动力学模拟表明，必须在孔上做功，以减少孔衬（S6）α-螺旋中的扭结，从而形成穿过并关闭通道的螺旋束。当孔隙关闭时，应变积累，随后驱动开口。我们还确定了突变的PVPV基序，导致在S6螺旋扭结的影响。最后，一个近似的上限上有多远的S4螺旋位移孔关闭估计。 电压门控性钾离子通道响应于跨膜电位的变化而开放和关闭，但其开放机制知之甚少。在这里，自由能分子动力学模拟表明，应变积累的孔隙关闭，随后驱动开放。
Voltage-gated potassium channels form potassium-selective pores in cell membranes. They open or close in response to changes in the transmembrane potential and are essential for generating action potentials, and thus for the functioning of heart and brain. While a mechanism for how these channels close has been proposed, it is not clear what drives their opening. Here we use free energy molecular dynamics simulations to show that work must be done on the pore to reduce the kink in the pore-lining (S6) α-helices, thereby forming the helix bundle crossing and closing the channel. Strain is built up as the pore closes, which subsequently drives opening. We also determine the effect of mutating the PVPV motif that causes the kink in the S6 helix. Finally, an approximate upper limit on how far the S4 helix is displaced as the pore closes is estimated. Voltage-gated potassium channels open and close in response to changes in transmembrane potential, but their opening mechanism is poorly understood. Here, free energy molecular dynamics simulations show that strain accumulates as the pore closes, which subsequently drives opening.
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影响因子：
16.2
作者：
Aggarwal, SK;MacKinnon, R
通讯作者：
MacKinnon, R
DOI：
10.1073/pnas.0711533105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Clayton, Gina M.;Altieri, Steve;Morais-Cabral, Joao H.
通讯作者：
Morais-Cabral, Joao H.
影响因子：
2.9
作者：
Denning, Elizabeth J.;Woolf, Thomas B.
通讯作者：
Woolf, Thomas B.
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