7PHH

Human voltage-gated potassium channel Kv3.1 (apo condition)

7PHH の概要

• エントリーDOI: 10.2210/pdb7phh/pdb
• EMDBエントリー: 13416
• 分子名称: Potassium voltage-gated channel, Shaw-related subfamily, member 1, 1,2-DIACYL-SN-GLYCERO-3-PHOSHOCHOLINE, ZINC ION, ... (4 entities in total)
• 機能のキーワード: channel, potassium channel, tetramer, voltage-gated, membrane protein, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 241690.65

構造登録者

Chi, G.,Venkaya, S.,Singh, N.K.,McKinley, G.,Mukhopadhyay, S.M.M.,Marsden, B.,MacLean, E.M.,Fernandez-Cid, A.,Pike, A.C.W.,Savva, C.,Ragan, T.J.,Burgess-Brown, N.A.,Duerr, K.L. (登録日: 2021-08-17, 公開日: 2022-03-02, 最終更新日: 2025-07-02)

主引用文献

Chi, G.,Liang, Q.,Sridhar, A.,Cowgill, J.B.,Sader, K.,Radjainia, M.,Qian, P.,Castro-Hartmann, P.,Venkaya, S.,Singh, N.K.,McKinley, G.,Fernandez-Cid, A.,Mukhopadhyay, S.M.M.,Burgess-Brown, N.A.,Delemotte, L.,Covarrubias, M.,Durr, K.L.
Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain.
Nat Commun, 13:4087-4087, 2022

PubMed Abstract: Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and mutational analyses, we identify several residues in the S4/S5 linker which influence the gating kinetics and an electrostatic interaction between acidic residues in α6 of T1 and R449 in the pore-flanking S6T helices. These findings provide insights into gating control and disease mechanisms and may guide strategies for the design of pharmaceutical drugs targeting Kv3 channels.

PubMed: 35840580
DOI: 10.1038/s41467-022-29594-w

実験手法

ELECTRON MICROSCOPY (3.2 Å)