Crystal structure and functional analysis of the HERG potassium channel N terminus: A eukaryotic PAS domain
Crystal structure and functional analysis of the HERG potassium channel N terminus: A eukaryotic PAS domain
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DOI：
10.1016/s0092-8674(00)81635-9
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发表时间：
1998-11-25
期刊：
影响因子：
64.5
通讯作者：
Mackinnon, R
中科院分区：
文献类型：
--
作者：
Cabral, JHM;Lee, A;Mackinnon, R
HERG电压依赖性K+通道在心脏电兴奋性中起作用，当其缺陷时，它是长QT综合征的一种形式的基础。我们确定了HERG K+通道n端畴的晶体结构，并利用电生理方法研究了其作为门控调节剂的作用。该结构域在结构上类似于细菌光传感器光活性黄色蛋白，并提供了真核生物PAS结构域的第一个三维模型。结构域表面的扫描诱变已经允许识别一个疏水“热点”，形成一个假定的与K+通道体紧密结合的界面。连接到通道上的结构域的存在减缓了失活的速度。鉴于PAS结构域在生物学中的作用，我们认为HERG n端结构域具有调控功能。
The HERG voltage-dependent K+ channel plays a role in cardiac electrical excitability, and when defective, it underlies one form of the long QT syndrome. We have determined the crystal structure of the HERG K+ channel N-terminal domain and studied its role as a modifier of gating using electrophysiological methods. The domain is similar in structure to a bacterial light sensor photoactive yellow protein and provides the first three-dimensional model of a eukaryotic PAS domain. Scanning mutagenesis of the domain surface has allowed the identification of a hydrophobic "hot spot" forming a putative interface with the body of the K+ channel to which it tightly binds. The presence, of the domain attached to the channel slows the rate of deactivation. Given the roles of PAS domains in biology, we propose that the HERG N-terminal domain has a regulatory function.