摘要
NaChBac is a bacterial voltage-gated sodium (Na-v) channel that shows sequence similarity to voltage-gated calcium channels. To understand the ion-permeation mechanism of Na-v channels, we combined molecular dynamics simulation, structural biology and electrophysiological approaches to investigate the recently determined structure of NavRh, a marine bacterial NaChBac ortholog. Two Na+ binding sites are identified in the selectivity filter (SF) in our simulations: The extracellular Na+ ion first approaches site 1 constituted by the side groups of Ser181 and Glu183, and then spontaneously arrives at the energetically more favorable site 2 formed by the carbonyl oxygens of Leu179 and Thr178. In contrast, Ca2+ ions are prone to being trapped by Glu183 at site 1, which then blocks the entrance of both Na+ and Ca2+ to the vestibule of the SF. In addition, Na+ permeates through the selective filter in an asymmetrical manner, a feature that resembles that of the mammalian Na-v orthologs. The study reported here provides insights into the mechanism of ion selectivity on Na+ over Ca2+ in mammalian Na-v channels.
- 出版日期2013-3
- 单位膜生物学国家重点实验室; 中国科学院; 中国科学院上海应用物理研究所; 清华大学