Title | Analysis of the selectivity filter of the voltage-gated sodium channel Na(v)Rh. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Zhang, X, Xia, M, Li, Y, Liu, H, Jiang, X, Ren, W, Wu, J, DeCaen, P, Yu, F, Huang, S, He, J, Clapham, DE, Yan, N, Gong, H |
Journal | Cell Res |
Volume | 23 |
Issue | 3 |
Pagination | 409-22 |
Date Published | 2013 Mar |
ISSN | 1748-7838 |
Keywords | Animals, Bacterial Proteins, Binding Sites, Electrophysiology, Molecular Dynamics Simulation, Potassium, Sodium, Sodium Channels, Voltage-Gated Sodium Channels |
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> |
DOI | 10.1038/cr.2012.173 |
Alternate Journal | Cell Res |
PubMed ID | 23247626 |
PubMed Central ID | PMC3587708 |
Grant List | P01 NS072040 / NS / NINDS NIH HHS / United States P30 HD018655 / HD / NICHD NIH HHS / United States T32 HL007572 / HL / NHLBI NIH HHS / United States |