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

Voltage-gated sodium (Na_v) channels are essential for the rapid depolarization of nerve and muscle¹, and are important drug targets². Determination of the structures of Na_v channels will shed light on ion channel mechanisms and facilitate potential clinical applications. A family of bacterial Na_v 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 Na_v 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 Na_v Rh is in an conformation. Comparison of Na_v Rh with Na_v Ab reveals considerable conformational rearrangements that may underlie the electromechanical coupling mechanism of voltage-gated channels.