Analysis of the selectivity filter of the voltage-gated sodium channel Na v Rh

Xu Zhang, Mengdie Xia, Yang Li, Huihui Liu, Xin Jiang, Wenlin Ren, Jianping Wu, Paul Decaen, Feng Yu, Sheng Huang, Jianhua He, David E. Clapham, Nieng Yan, Haipeng Gong

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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 Na v Rh, 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 Na v orthologs. The study reported here provides insights into the mechanism of ion selectivity on Na + over Ca 2+ in mammalian Na v channels.

Original languageEnglish (US)
Pages (from-to)409-422
Number of pages14
JournalCell Research
Volume23
Issue number3
DOIs
StatePublished - Mar 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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