Morais-Cabral J H, Zhou Y, MacKinnon R
Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06520, USA.
Nature. 2001 Nov 1;414(6859):37-42. doi: 10.1038/35102000.
The K+ selectivity filter catalyses the dehydration, transfer and rehydration of a K+ ion in about ten nanoseconds. This physical process is central to the production of electrical signals in biology. Here we show how nearly diffusion-limited rates are achieved, by analysing ion conduction and the corresponding crystallographic ion distribution in the selectivity filter of the KcsA K+ channel. Measurements with K+ and its slightly larger analogue, Rb+, lead us to conclude that the selectivity filter usually contains two K+ ions separated by one water molecule. The two ions move in a concerted fashion between two configurations, K+-water-K+-water (1,3 configuration) and water-K+-water-K+ (2,4 configuration), until a third ion enters, displacing the ion on the opposite side of the queue. For K+, the energy difference between the 1,3 and 2,4 configurations is close to zero, the condition of maximum conduction rate. The energetic balance between these configurations is a clear example of evolutionary optimization of protein function.
钾离子选择性过滤器在大约十纳秒内催化钾离子的脱水、转移和再水合过程。这一物理过程是生物体内电信号产生的核心。在此,我们通过分析钾离子通道KcsA的选择性过滤器中的离子传导以及相应的晶体学离子分布,展示了近乎扩散极限的速率是如何实现的。对钾离子及其稍大的类似物铷离子的测量结果使我们得出结论,选择性过滤器通常包含两个被一个水分子隔开的钾离子。这两个离子以协同的方式在两种构型之间移动,即K⁺-水-K⁺-水(1,3构型)和水-K⁺-水-K⁺(2,4构型),直到第三个离子进入,取代队列中另一侧的离子。对于钾离子,1,3构型和2,4构型之间的能量差接近于零,这是最大传导速率的条件。这些构型之间的能量平衡是蛋白质功能进化优化的一个明显例子。