@article{168041,
  keywords = {Humans, drug discovery, Mutation, Amino Acid Sequence, Cryoelectron Microscopy, HEK293 Cells, Protein Domains, Allosteric Regulation, Channelopathies, NAV1.4 Voltage-Gated Sodium Channel, Voltage-Gated Sodium Channel beta-4 Subunit},
  author = {Xiaojing Pan and Zhangqiang Li and Qiang Zhou and Huaizong Shen and Kun Wu and Xiaoshuang Huang and Jiaofeng Chen and Juanrong Zhang and Xuechen Zhu and Jianlin Lei and Wei Xiong and Haipeng Gong and Bailong Xiao and Nieng Yan},
  title = {Structure of the human voltage-gated sodium channel Na1.4 in complex with β1},
  abstract = {<p>Voltage-gated sodium (Na) 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 Na channel has hampered mechanistic understanding. Here, we report the cryo-electron microscopy structure of the human Na1.4-β1 complex at 3.2-{\r A} resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 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 Na channels. The structure provides a path toward mechanistic investigation of Na channels and drug discovery for Na channelopathies.</p>
},
  year = {2018},
  journal = {Science},
  volume = {362},
  month = {10/2018},
  issn = {1095-9203},
  doi = {10.1126/science.aau2486},
  language = {eng},
}