A gating model for the archeal voltage-dependent K(+) channel KvAP in DPhPC and POPE:POPG decane lipid bilayers.

A gating model for the archeal voltage-dependent K(+) channel KvAP in DPhPC and POPE:POPG decane lipid bilayers.
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DOI:
10.1016/j.jmb.2009.05.062
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发表时间:
2009-07-31
影响因子:
5.6
通讯作者:
MacKinnon, Roderick
MacKinnon, Roderick
中科院分区:
生物学2区
文献类型:
--
作者:
Schmidt, Daniel;Cross, Samuel R.;MacKinnon, Roderick

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电压依赖性K+(Kv)通道是神经和肌肉兴奋性的基础。KvAP是一种特性良好的原始型Kv通道,已被广泛用于研究Kv通道的生物化学、生物物理和结构的多个方面。在这项研究中,发展了一个最小的动力学门控模型的KvAP功能在两个不同的磷脂十烷双层。在大多数方面,Kvap门控类似于研究得很好的真核细胞的Shaker Kv通道:构象变化发生在四个电压传感器内,随后是孔道开放。与Shaker不同,KvAP具有可从通道的预打开状态访问的非激活状态。改变膜的脂质成分会影响模型中的多个门控转变,但最显著的是从失活中恢复的速度。如果VSTx1仅与电压传感器的去极化构象结合,则最容易解释VSTx1毒素对VSTx1的抑制作用。通过延迟电压传感器返回到超极化构象,VSTx1有利于KvAP的失活状态。
Voltage-dependent K+ (Kv) channels form the basis of the excitability of nerves and muscles. KvAP is a well-characterized archeal Kv channel that has been widely used to investigate many aspects of Kv channel biochemistry, biophysics and structure. In this study a minimal kinetic gating model for KvAP function in two different phospholipid decane bilayers is developed. In most aspects KvAP gating is similar to the well-studied eukaryotic Shaker Kv channel: conformational changes occur within four voltage sensors followed by pore opening. Unlike Shaker, KvAP possesses an inactivated state that is accessible from the pre-open state of the channel. Changing the lipid composition of the membrane influences multiple gating transitions in the model, but most dramatically the rate of recovery from inactivation. Inhibition by the voltage sensor toxin VSTx1 is most easily explained if VSTx1 binds only to the depolarized conformation of the voltage sensor. By delaying the voltage sensor’s return to the hyperpolarized conformation VSTx1 favors the inactivated state of KvAP.
DOI: 10.1073/pnas.0810187105
发表时间: 2008-12-09
影响因子: 11.1
作者:
Schmidt, Daniel;MacKinnon, Roderick
通讯作者: MacKinnon, Roderick
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发表时间: 2003-03-13
期刊: NATURE
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影响因子: 5.5
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HODGKIN, AL;HUXLEY, AF
通讯作者: HUXLEY, AF
DOI: 10.1016/s0006-3495(94)80517-x
发表时间: 1994-08-01
影响因子: 3.4
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通讯作者: LEVITAN, IB
振动钾通道门控。 II:激活途径中的过渡。
DOI: 10.1085/jgp.103.2.279
发表时间: 1994-02
期刊: The Journal of general physiology
影响因子: --
作者:
Zagotta WN;Hoshi T;Dittman J;Aldrich RW
通讯作者: Aldrich RW