Structure basis for the activation of KCNQ2 by endogenous and exogenous ligands.

Zhao et al. report cryo-EM structures of human KCNQ2 in complex with QO-58 and QO-83 in multiple conformations, with or without PIP2. Together with electrophysiological and computational analyses, these structures provide insight into the channel’s activation mechanism and support the rational design of targeted anti-epileptic therapies.