@article{168341,
  keywords = {Animals, Molecular Dynamics Simulation, Bacterial Proteins, Binding Sites, Electrophysiology, Potassium, voltage-gated sodium channels, Sodium, Sodium Channels},
  author = {Xu Zhang and Mengdie Xia and Yang Li and Huihui Liu and Xin Jiang and Wenlin Ren and Jianping Wu and Paul DeCaen and Feng Yu and Sheng Huang and Jianhua He and David Clapham and Nieng Yan and Haipeng Gong},
  title = {Analysis of the selectivity filter of the voltage-gated sodium channel Na(v)Rh},
  abstract = {<p>NaChBac is a bacterial voltage-gated sodium (Nav) channel that shows sequence similarity to voltage-gated calcium channels. To understand the ion-permeation mechanism of Nav 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, Ca(2+) ions are prone to being trapped by Glu183 at site 1, which then blocks the entrance of both Na(+) and Ca(2+) 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 Nav orthologs. The study reported here provides insights into the mechanism of ion selectivity on Na(+) over Ca(2+) in mammalian Nav channels.</p>
},
  year = {2013},
  journal = {Cell Res},
  volume = {23},
  pages = {409-22},
  month = {03/2013},
  issn = {1748-7838},
  doi = {10.1038/cr.2012.173},
  language = {eng},
}