资源环境科技发展态势分析平台

The voltage-gated sodium channel Na(v)1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo-electron microscopy structure of human Na(v)1.2 bound to a peptidic pore blocker, the m-conotoxin KIIIA, in the presence of an auxiliary subunit, beta 2, to an overall resolution of 3.0 angstroms. The immunoglobulin domain of beta 2 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 Lys7 at the entrance to the selectivity filter. Many interacting residues are specific to Na(v)1.2, revealing a molecular basis for KIIIA specificity. The structure establishes a framework for the rational design of subtype-specific blockers for Na-v channels.