Cryo-EM Structure of the Mammalian Kv2.1 Delayed-Rectifier Potassium Channel Reveals Insight into Gating Mechanisms and Epileptic Encephalopathy

The Kv2.1 delayed-rectifier K+ channel is one of the most abundant ion channels in the mammalian brain, where it functions as a slowly activating and inactivating voltage-activated K+ ion selective channel that is critical for neuronal activity, with mutations causing epileptic encephalopathy. Here we solve the structure of the Kv2.1 channel in a membrane environment using cryogenic electron microscopy at 2.9 Å resolution. Kv2.1 exhibits a domain-swapped relationship between voltage-sensing and pore domains, with voltage-sensing domains in an activated state and the pore in an open conducting state.