Neutron Scattering Division, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37831, USA.
Acta Crystallogr D Struct Biol. 2020 Apr 1;76(Pt 4):326-331. doi: 10.1107/S2059798320003599.
The study of ion channels dates back to the 1950s and the groundbreaking electrophysiology work of Hodgin and Huxley, who used giant squid axons to probe how action potentials in neurons were initiated and propagated. More recently, several experiments using different structural biology techniques and approaches have been conducted to try to understand how potassium ions permeate through the selectivity filter of potassium ion channels. Two mechanisms of permeation have been proposed, and each of the two mechanisms is supported by different experiments. The key structural biology experiments conducted so far to try to understand how ion permeation takes place in potassium ion channels are reviewed and discussed. Protein crystallography has made, and continues to make, key contributions in this field, often through the use of anomalous scattering. Other structural biology techniques used to study the contents of the selectivity filter include solid-state nuclear magnetic resonance and two-dimensional infrared spectroscopy, both of which make clever use of isotopic labeling techniques, while molecular-dynamics simulations of ion flow through the selectivity filter have been enabled by the growing number of potassium ion channel structures deposited in the Protein Data Bank.
离子通道的研究可以追溯到 20 世纪 50 年代,霍奇金和赫胥黎的开创性电生理学工作使用巨型乌贼轴突来探究神经元中的动作电位是如何发起和传播的。最近,使用不同的结构生物学技术和方法进行了几项实验,试图了解钾离子如何通过钾离子通道的选择性过滤器渗透。已经提出了两种渗透机制,并且每种机制都得到了不同实验的支持。迄今为止,为了试图理解钾离子通道中离子渗透是如何发生的,进行了关键的结构生物学实验,并对这些实验进行了综述和讨论。蛋白质晶体学在该领域做出了,并将继续做出关键贡献,通常是通过使用异常散射。用于研究选择性过滤器内容的其他结构生物学技术包括固态核磁共振和二维红外光谱,这两种技术都巧妙地利用了同位素标记技术,而通过越来越多的钾离子通道结构储存在蛋白质数据库中,使得通过选择性过滤器的离子流的分子动力学模拟成为可能。