Structure of the Na_v1.4-β1 Complex from Electric Eel.

Abstract

Voltage-gated sodium (Na_v) channels initiate and propagate action potentials. Here, we present the cryo-EM structure of EeNa_v1.4, the Na_v channel from electric eel, in complex with the β1 subunit at 4.0 Å resolution. The immunoglobulin domain of β1 docks onto the extracellular L5_I and L6_IV loops of EeNa_v1.4 via extensive polar interactions, and the single transmembrane helix interacts with the third voltage-sensing domain (VSD_III). 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 Na_vPaS 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.