|Title||Structure of the Nav1.4-β1 Complex from Electric Eel.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Yan, Z, Zhou, Q, Wang, L, Wu, J, Zhao, Y, Huang, G, Peng, W, Shen, H, Lei, J, Yan, N|
|Date Published||2017 Jul 27|
|Keywords||Amino Acid Sequence, Animals, Cryoelectron Microscopy, Electrophorus, Fish Proteins, Models, Molecular, Protein Domains, Sequence Alignment, Voltage-Gated Sodium Channels|
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.