Structure Report for: 7UKH

only a small fragment of DPP6 in structure

Title: Activation and closed-state inactivation mechanisms of the human voltage-gated K(V)4 channel complexes
Ye W, Zhao H, Dai Y, Wang Y, Lo YH, Jan LY, Lee CH
Ref: Mol Cell, :, 2022 : PubMed
Abstract


ESTHER: Ye_2022_Mol.Cell_S1097-2765_00395
PubMedSearch: Ye 2022 Mol.Cell S1097-2765 00395
PubMedID: 35597238

Abstract

The voltage-gated ion channel activity depends on both activation (transition from the resting state to the open state) and inactivation. Inactivation is a self-restraint mechanism to limit ion conduction and is as crucial to membrane excitability as activation. Inactivation can occur when the channel is open or closed. Although open-state inactivation is well understood, the molecular basis of closed-state inactivation has remained elusive. We report cryo-EM structures of human K(V)4.2 channel complexes in inactivated, open, and closed states. Closed-state inactivation of K(V)4 involves an unprecedented symmetry breakdown for pore closure by only two of the four S4-S5 linkers, distinct from known mechanisms of open-state inactivation. We further capture K(V)4 in a putative resting state, revealing how voltage sensor movements control the pore. Moreover, our structures provide insights regarding channel modulation by KChIP2 and DPP6 auxiliary subunits. Our findings elucidate mechanisms of closed-state inactivation and voltage-dependent activation of the K(V)4 channel.