Editing of human K(V)1.1 channel mRNAs disrupts binding of the N-terminus tip at the intracellular cavity.
Editing of human K(V)1.1 channel mRNAs disrupts binding of the N-terminus tip at the intracellular cavity.
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DOI：
10.1038/ncomms1446
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发表时间：
2011-08-16
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
在神经系统中，A→I RNA编辑在调节神经元兴奋性方面具有重要作用。配体门控膜受体、突触蛋白以及离子通道是RNA编辑重新编码的靶点。尽管在哺乳动物大脑中已经发现了大量的编辑位点，但人们对它们引起的功能改变知之甚少，更不知道它们如何改变蛋白质功能的机制基础。我们之前已经表明，RNA编辑事件（I400 V）改变了人KV 1.1的内部渗透途径，改变了快速失活的动力学。在这里，我们表明，通道的失活门进入深入到离子渗透途径和非常尖端建立一个直接的疏水相互作用与编辑的位置。通过将I转化为V，相互作用的亲密度降低，允许失活门以更快的动力学解除结合。 RNA编辑在调节神经元兴奋性中是重要的，并且已经显示特定的编辑事件改变电压门控钾通道的渗透途径。Gonzalez等人发现，通道失活门的尖端与编辑的位置产生直接的疏水相互作用。
In the nervous system, A→I RNA editing has an important role in regulating neuronal excitability. Ligand-gated membrane receptors, synaptic proteins, as well as ion channels, are targets for recoding by RNA editing. Although scores of editing sites have been identified in the mammalian brain, little is known about the functional alterations that they cause, and even less about the mechanistic underpinnings of how they change protein function. We have previously shown that an RNA editing event (I400 V) alters the inner permeation pathway of human KV1.1, modifying the kinetics of fast inactivation. Here we show that the channel's inactivation gate enters deep into the ion permeation pathway and the very tip establishes a direct hydrophobic interaction with the edited position. By converting I to V, the intimacy of the interaction is reduced, allowing the inactivation gate to unbind with much faster kinetics. RNA editing is important in regulating neuronal excitability, and a specific editing event has been shown to alter the permeation pathway of voltage-gate potassium channels. Gonzalez et al. find that the tip of the channel's inactivation gate makes a direct hydrophobic interaction with the edited position.
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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
影响因子：
5.5
作者：
GUSTAFSSON, B;LINDSTROM, S;ZANGGER, P
通讯作者：
ZANGGER, P
影响因子：
11.4
作者：
Jing, J;Chikvashvili, D;Lotan, I
通讯作者：
Lotan, I
影响因子：
16.8
作者：
Bhalla, T;Rosenthal, JJC;Reenan, R
通讯作者：
Reenan, R