Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel
Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel
复制标题
DOI：
10.1073/pnas.1515965112
复制
发表时间：
2015-12-15
影响因子：
11.1
通讯作者：
Henzler-Wildman, Katherine A.
中科院分区：
文献类型：
--
作者：
Brettmann, Joshua B.;Urusova, Darya;Henzler-Wildman, Katherine A.
由内栅和选择性过滤器之间的功能耦合引起的通量依赖性失活在离子通道中广泛存在。这种耦合的结构基础仅在KcsA中得到了很好的表征。在这里，我们展示了核磁共振数据，证明了细菌非选择性阳离子通道（NaK）中选择性过滤器和细胞内收缩点之间的结构和动态耦合。这种跨膜变构通信在结构上一定不同于KcsA，因为NaK选择性滤波器在低阳离子条件下不会坍塌。非选择性NaK和钾选择性NaK2K的核磁共振光谱比较表明，选择性过滤器中离子结合位点的数量改变了整个通道中结构态的平衡分布。这一发现是出乎意料的，因为NaK和NaK2K的晶体结构几乎完全相同，而不是在选择性滤波器附近。我们的研究结果强调了选择性过滤器和通道支架之间的紧密结构和动态耦合，这对通道功能具有重要意义。NaK为研究离子传导和通道门控之间的生理本质联系提供了一个独特的模型。
Flux-dependent inactivation that arises from functional coupling between the inner gate and the selectivity filter is widespread in ion channels. The structural basis of this coupling has only been well characterized in KcsA. Here we present NMR data demonstrating structural and dynamic coupling between the selectivity filter and intracellular constriction point in the bacterial nonselective cation channel, NaK. This transmembrane allosteric communication must be structurally different from KcsA because the NaK selectivity filter does not collapse under low-cation conditions. Comparison of NMR spectra of the nonselective NaK and potassium-selective NaK2K indicates that the number of ion binding sites in the selectivity filter shifts the equilibrium distribution of structural states throughout the channel. This finding was unexpected given the nearly identical crystal structure of NaK and NaK2K outside the immediate vicinity of the selectivity filter. Our results highlight the tight structural and dynamic coupling between the selectivity filter and the channel scaffold, which has significant implications for channel function. NaK offers a distinct model to study the physiologically essential connection between ion conduction and channel gating.