Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1

Xiaojing Pan, Zhangqiang Li, Qiang Zhou, Huaizong Shen, Kun Wu, Xiaoshuang Huang, Jiaofeng Chen, Juanrong Zhang, Xuechen Zhu, Jianlin Lei, Wei Xiong, Haipeng Gong, Bailong Xiao, Nieng Yan

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Voltage-gated sodium (Nav) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Nav channel has hampered mechanistic understanding. Here, we report the cryo-electron microscopy structure of the human Nav1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the b1 subunit, providing insight into the molecular basis for Na+ permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Nav channels. The structure provides a path toward mechanistic investigation of Nav channels and drug discovery for Nav channelopathies.

Original languageEnglish (US)
Article numbereaau2486
JournalScience
Volume362
Issue number6412
DOIs
StatePublished - Oct 19 2018

All Science Journal Classification (ASJC) codes

  • General

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