Treptow Werner, Tarek Mounir
UMR Structure et Réactivité des Systèmes Moléculaires Complexes, Nancy-University, Centre National de la Recherche Scientifique, Nancy, France.
Biophys J. 2006 Nov 15;91(10):L81-3. doi: 10.1529/biophysj.106.095992. Epub 2006 Sep 15.
Potassium channels display a high conservation of sequence of the selectivity filter (SF), yet nature has designed a variety of channels that present a wide range of absolute rates of K(+) permeation. In KcsA, the structural archetype for K channels, under physiological concentrations, two K(+) ions reside in the SF in configurations 1,3 (up state) and 2,4 (down state) and ion conduction is believed to follow a throughput cycle involving a transition between these states. Using free-energy calculations of KcsA, Kv1.2, and mutant channels, we show that this transition is characterized by a channel-dependent energy barrier. This barrier is strongly influenced by the charges partitioned along the sequence of each channel. These results unveil therefore how, for similar structures of the SF, the rate of K(+) turnover may be fine-tuned within the family of potassium channels.
钾通道在选择性过滤器（SF）的序列上表现出高度保守性，但大自然设计了多种通道，这些通道呈现出广泛的钾离子（K⁺）通透绝对速率。在钾通道的结构原型KcsA中，在生理浓度下，两个K⁺离子以1,3构型（上状态）和2,4构型（下状态）存在于SF中，并且离子传导被认为遵循一个涉及这些状态之间转变的通量循环。通过对KcsA、Kv1.2和突变通道进行自由能计算，我们表明这种转变的特征是存在一个依赖于通道的能垒。这个能垒受到沿每个通道序列分布的电荷的强烈影响。因此，这些结果揭示了对于类似结构的SF，钾离子周转速率如何在钾通道家族中进行微调。
