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KCNE1 调节 KCNQ1 钾通道结构基础的工作模型。

Working model for the structural basis for KCNE1 modulation of the KCNQ1 potassium channel.

机构信息

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-8725, USA.

出版信息

Curr Opin Struct Biol. 2011 Apr;21(2):283-91. doi: 10.1016/j.sbi.2011.01.001. Epub 2011 Feb 4.

Abstract

The voltage-gated potassium channel KCNQ1 (Kv7.1) is modulated by KCNE1 (minK) to generate the I(Ks) current crucial to heartbeat. Defects in either protein result in serious cardiac arrhythmias. Recently developed structural models of the open and closed state KCNQ1/KCNE1 complexes offer a compelling explanation for how KCNE1 slows channel opening and provides a platform from which to refine and test hypotheses for other aspects of KCNE1 modulation. These working models were developed using an integrative approach based on results from nuclear magnetic resonance spectroscopy, electrophysiology, biochemistry, and computational methods-an approach that can be applied iteratively for model testing and revision. We present a critical review of these structural models, illustrating the strengths and challenges of the integrative approach.

摘要

电压门控钾通道 KCNQ1(Kv7.1)与 KCNE1(minK)相互作用调节以产生对心跳至关重要的 I(Ks)电流。这两种蛋白的任何缺陷都会导致严重的心律失常。最近开发的开放和关闭状态 KCNQ1/KCNE1 复合物的结构模型为 KCNE1 如何减缓通道开放提供了令人信服的解释,并为其他 KCNE1 调节方面的假设提供了一个细化和测试的平台。这些工作模型是使用基于核磁共振波谱学、电生理学、生物化学和计算方法的综合方法开发的,该方法可用于模型测试和修正的迭代。我们对这些结构模型进行了批判性回顾,说明了综合方法的优势和挑战。

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本文引用的文献

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Stoichiometry of the KCNQ1 - KCNE1 ion channel complex.KCNQ1-KCNE1 离子通道复合物的化学计量。
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Science. 2010 Apr 2;328(5974):67-73. doi: 10.1126/science.1185954.

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