Sansom Mark S P, Shrivastava Indira H, Bright Joanne N, Tate John, Capener Charlotte E, Biggin Philip C
Laboratory of Molecular Biophysics, Department of Biochemistry, The University of Oxford, The Rex Richards Building, South Parks Road, Oxford, UK.
Biochim Biophys Acta. 2002 Oct 11;1565(2):294-307. doi: 10.1016/s0005-2736(02)00576-x.
Potassium channels have been studied intensively in terms of the relationship between molecular structure and physiological function. They provide an opportunity to integrate structural and computational studies in order to arrive at an atomic resolution description of mechanism. We review recent progress in K channel structural studies, focussing on the bacterial channel KcsA. Structural studies can be extended via use of computational (i.e. molecular simulation) approaches in order to provide a perspective on aspects of channel function such as permeation, selectivity, block and gating. Results from molecular dynamics simulations are shown to be in good agreement with recent structural studies of KcsA in terms of the interactions of K(+) ions with binding sites within the selectivity filter of the channel, and in revealing the importance of filter flexibility in channel function. We discuss how the KcsA structure may be used as a template for developing structural models of other families of K channels. Progress in this area is explored via two examples: inward rectifier (Kir) and voltage-gated (Kv) potassium channels. A brief account of structural studies of ancillary domains and subunits of K channels is provided.
关于分子结构与生理功能之间的关系，人们对钾通道进行了深入研究。它们为整合结构研究和计算研究提供了契机，以便获得对机制的原子分辨率描述。我们回顾了钾通道结构研究的最新进展，重点关注细菌通道KcsA。结构研究可以通过使用计算（即分子模拟）方法来扩展，以便对通道功能的各个方面，如通透、选择性、阻断和门控，提供一个视角。分子动力学模拟的结果表明，在钾离子与通道选择性过滤器内结合位点的相互作用方面，以及在揭示过滤器灵活性在通道功能中的重要性方面，与KcsA最近的结构研究结果高度一致。我们讨论了KcsA结构如何用作开发其他钾通道家族结构模型的模板。通过两个例子探讨了该领域的进展：内向整流（Kir）和电压门控（Kv）钾通道。还简要介绍了钾通道辅助结构域和亚基的结构研究情况。
