Research Article

Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution

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Science  09 Feb 2017:

DOI: 10.1126/science.aal4326

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Abstract

Voltage-gated sodium (Nav) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple pharmaceutical drugs and natural toxins. Here, we report the cryo-EM structure of a putative Nav channel from American cockroach (designated NavPaS) at 3.8-Å resolution. The voltage sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond-stabilized extracellular loops. On the cytoplasmic side, a conserved amino terminal domain is placed below VSDI and a carboxy terminal domain binds to the III-IV linker. The structure of NavPaS establishes an important foundation for understanding function and disease mechanism of Nav and related Cav channels.

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