Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel

Xu Zhang, Wenlin Ren, Paul Decaen, Chuangye Yan, Xiao Tao, Lin Tang, Jingjing Wang, Kazuya Hasegawa, Takashi Kumasaka, Jianhua He, Jiawei Wang, David E. Clapham, Nieng Yan

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Abstract

Voltage-gated sodium (Nav) channels are essential for the rapid depolarization of nerve and muscle1, and are important drug targets2. Determination of the structures of Nav channels will shed light on ion channel mechanisms and facilitate potential clinical applications. A family of bacterial Nav channels, exemplified by the Na+-selective channel of bacteria (NaChBac)3, provides a useful model system for structureg-function analysis. Here we report the crystal structure of Nav Rh, a NaChBac orthologue from the marine alphaproteobacterium HIMB114 (Rickettsiales sp. HIMB114; denoted Rh), at 3.05 Å resolution. The channel comprises an asymmetric tetramer. The carbonyl oxygen atoms of Thr 178 and Leu 179 constitute an inner site within the selectivity filter where a hydrated Ca2+ resides in the crystal structure. The outer mouth of the Na+ selectivity filter, defined by Ser 181 and Glu 183, is closed, as is the activation gate at the intracellular side of the pore. The voltage sensors adopt a depolarized conformation in which all the gating charges are exposed to the extracellular environment. We propose that Nav Rh is in an conformation. Comparison of Nav Rh with Nav Ab reveals considerable conformational rearrangements that may underlie the electromechanical coupling mechanism of voltage-gated channels.

Original languageEnglish (US)
Pages (from-to)130-134
Number of pages5
JournalNature
Volume486
Issue number7401
DOIs
StatePublished - Jun 7 2012

All Science Journal Classification (ASJC) codes

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    Zhang, X., Ren, W., Decaen, P., Yan, C., Tao, X., Tang, L., Wang, J., Hasegawa, K., Kumasaka, T., He, J., Wang, J., Clapham, D. E., & Yan, N. (2012). Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature, 486(7401), 130-134. https://doi.org/10.1038/nature11054