Structure of the Nav1.4-β1 Complex from Electric Eel

Publication date: Available online 20 July 2017
Source:Cell
Author(s): Zhen Yan, Qiang Zhou, Lin Wang, Jianping Wu, Yanyu Zhao, Gaoxingyu Huang, Wei Peng, Huaizong Shen, Jianlin Lei, Nieng Yan
Voltage-gated sodium (Nav) channels initiate and propagate action potentials. Here, we present the cryo-EM structure of EeNav1.4, the Nav channel from electric eel, in complex with the β1 subunit at 4.0 Å resolution. The immunoglobulin domain of β1 docks onto the extracellular L5I and L6IV loops of EeNav1.4 via extensive polar interactions, and the single transmembrane helix interacts with the third voltage-sensing domain (VSDIII). The VSDs exhibit “up” conformations, while the intracellular gate of the pore domain is kept open by a digitonin-like molecule. Structural comparison with closed NavPaS shows that the outward transfer of gating charges is coupled to the iris-like pore domain dilation through intricate force transmissions involving multiple channel segments. The IFM fast inactivation motif on the III-IV linker is plugged into the corner enclosed by the outer S4-S5 and inner S6 segments in repeats III and IV, suggesting a potential allosteric blocking mechanism for fast inactivation.

Graphical abstract

Teaser

Structural analysis of the eel Nav1.4 channel offers insights into the electromechanical coupling mechanism of voltage-gated sodium channels.


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