@article{168111,
  keywords = {Protein Conformation, Humans, Amino Acid Sequence, Cryoelectron Microscopy, HEK293 Cells, Voltage-Gated Sodium Channel Blockers, Voltage-Gated Sodium Channel beta-2 Subunit, Conotoxins, NAV1.2 Voltage-Gated Sodium Channel},
  author = {Xiaojing Pan and Zhangqiang Li and Xiaoshuang Huang and Gaoxingyu Huang and Shuai Gao and Huaizong Shen and Lei Liu and Jianlin Lei and Nieng Yan},
  title = {Molecular basis for pore blockade of human Na channel Na1.2 by the μ-conotoxin KIIIA},
  abstract = {<p>The voltage-gated sodium channel Na1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo-electron microscopy structure of human Na1.2 bound to a peptidic pore blocker, the μ-conotoxin KIIIA, in the presence of an auxiliary subunit, β2, to an overall resolution of 3.0 angstroms. The immunoglobulin domain of β2 interacts with the shoulder of the pore domain through a disulfide bond. The 16-residue KIIIA interacts with the extracellular segments in repeats I to III, placing Lys at the entrance to the selectivity filter. Many interacting residues are specific to Na1.2, revealing a molecular basis for KIIIA specificity. The structure establishes a framework for the rational design of subtype-specific blockers for Na channels.</p>
},
  year = {2019},
  journal = {Science},
  volume = {363},
  pages = {1309-1313},
  month = {03/2019},
  issn = {1095-9203},
  doi = {10.1126/science.aaw2999},
  language = {eng},
}