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

Zhen Yan, Qiang Zhou, Lin Wang, Jianping Wu, Yanyu Zhao, Gaoxingyu Huang, Wei Peng, Huaizong Shen, Jianlin Lei, Nieng Yan

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)470-482.e11
JournalCell
Volume170
Issue number3
DOIs
StatePublished - Jul 27 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

  • Na channels
  • Na1.4
  • cryo-EM
  • electromechanical coupling
  • fast inactivation
  • structural biology
  • the beta-1 subunit
  • voltage-gated sodium channels

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  • Cite this

    Yan, Z., Zhou, Q., Wang, L., Wu, J., Zhao, Y., Huang, G., Peng, W., Shen, H., Lei, J., & Yan, N. (2017). Structure of the Nav1.4-β1 Complex from Electric Eel. Cell, 170(3), 470-482.e11. https://doi.org/10.1016/j.cell.2017.06.039