7UKE

Human Kv4.2-KChIP2 channel complex in an intermediate state, transmembrane region

Summary for 7UKE

• Entry DOI: 10.2210/pdb7uke/pdb
• EMDB information: 26575 26576 26577 26578
• Descriptor: Potassium voltage-gated channel subfamily D member 2, POTASSIUM ION (2 entities in total)
• Functional Keywords: potassium channel complex, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 236353.72

Authors

Zhao, H.,Dai, Y.,Lee, C.H. (deposition date: 2022-04-01, release date: 2022-06-29, Last modification date: 2024-02-14)

Primary citation

Ye, W.,Zhao, H.,Dai, Y.,Wang, Y.,Lo, Y.H.,Jan, L.Y.,Lee, C.H.
Activation and closed-state inactivation mechanisms of the human voltage-gated K V 4 channel complexes.
Mol.Cell, 82:2427-, 2022

PubMed 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 K4.2 channel complexes in inactivated, open, and closed states. Closed-state inactivation of K4 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 K4 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 K4 channel.

PubMed: 35597238
DOI: 10.1016/j.molcel.2022.04.032

Experimental method

ELECTRON MICROSCOPY (3.01 Å)