Title : Molecular basis for pore blockade of human Na+ channel
Nav1.2 by the μ-conotoxin KIIIA
Abstract :
- The voltage-gated sodium channel Nav1.2 is responsible for the initiation and propagation of action potentials in the central nervous system
- We report the cryo-electron microscopy structure of human Nav1.2 bound to a peptidic pore blocker, the μ-conotoxin KIIIA, in the presence of an auxiliary subunit, β 2 , to an overall resolution of 3.0 angstroms
- The immunoglobulin domain of β 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 Nav1.2 , revealing a molecular basis for KIIIA specificity
- The structure establishes a framework for the rational design of subtype-specific blockers for Nav channels
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):