文章基本信息

标题：Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel
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作者：Joshua B. Brettmann ; Darya Urusova ; Marco Tonelli 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：50
页码：15366-15371
DOI：10.1073/pnas.1515965112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificancePore domains of ion channels form the ion conduction pathway and thus control the identity and flux of ions across the membrane. Flux-dependent inactivation suggests that these two functions are connected, with allosteric linkage between the selectivity filter and inner gate. This study uses solution NMR to investigate structural and dynamic features of ion selectivity and coupling between the gates in the small bacterial channel NaK. NaK is a nonselective cation channel and is homologous to several eukaryotic channels that are not well modeled by KcsA. Our results show a previously unexpected dynamic coupling between the selectivity filter and inner gate in NaK. This suggests that such transmembrane communication is widespread and occurs through distinct mechanisms in diverse channels. 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.
关键词：solution NMR ; ion channels ; membrane protein ; protein dynamics