7TCP

Structure of Xenopus KCNQ1-CaM

7TCP の概要

• エントリーDOI: 10.2210/pdb7tcp/pdb
• EMDBエントリー: 25813 25816
• 分子名称: Potassium voltage-gated channel subfamily KQT member 1, Calmodulin-1, CALCIUM ION (3 entities in total)
• 機能のキーワード: ion channel, transport protein
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 318544.71

構造登録者

Willegems, K.,Kyriakis, E.,Van Petegem, F.,Eldstrom, J.,Fedida, D. (登録日: 2021-12-27, 公開日: 2022-07-06, 最終更新日: 2025-05-21)

主引用文献

Willegems, K.,Eldstrom, J.,Kyriakis, E.,Ataei, F.,Sahakyan, H.,Dou, Y.,Russo, S.,Van Petegem, F.,Fedida, D.
Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277.
Nat Commun, 13:3760-3760, 2022

PubMed Abstract: The KCNQ1 ion channel plays critical physiological roles in electrical excitability and K recycling in organs including the heart, brain, and gut. Loss of function is relatively common and can cause sudden arrhythmic death, sudden infant death, epilepsy and deafness. Here, we report cryogenic electron microscopic (cryo-EM) structures of Xenopus KCNQ1 bound to Ca/Calmodulin, with and without the KCNQ1 channel activator, ML277. A single binding site for ML277 was identified, localized to a pocket lined by the S4-S5 linker, S5 and S6 helices of two separate subunits. Several pocket residues are not conserved in other KCNQ isoforms, explaining specificity. MD simulations and point mutations support this binding location for ML277 in open and closed channels and reveal that prevention of inactivation is an important component of the activator effect. Our work provides direction for therapeutic intervention targeting KCNQ1 loss of function pathologies including long QT interval syndrome and seizures.

PubMed: 35768468
DOI: 10.1038/s41467-022-31526-7

実験手法

ELECTRON MICROSCOPY (3.84 Å)