Morais Cabral J H, Lee A, Cohen S L, Chait B T, Li M, Mackinnon R
Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, New York 10021, USA.
Cell. 1998 Nov 25;95(5):649-55. doi: 10.1016/s0092-8674(00)81635-9.
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.
HERG电压依赖性钾离子通道在心脏电兴奋性中发挥作用，当其出现缺陷时，是长QT综合征的一种形式的基础。我们已经确定了HERG钾离子通道N端结构域的晶体结构，并使用电生理方法研究了其作为门控修饰剂的作用。该结构域在结构上与细菌光传感器光敏黄色蛋白相似，并提供了真核生物PAS结构域的第一个三维模型。对该结构域表面的扫描诱变已使我们能够识别出一个疏水“热点”，它形成了一个与紧密结合的钾离子通道主体的假定界面。连接到通道上的该结构域的存在减缓了失活速率。鉴于PAS结构域在生物学中的作用，我们提出HERG N端结构域具有调节功能。
