9G9X

Structure of the human two pore domain potassium ion channel TASK-1 (K2P3.1)

9G9X の概要

• エントリーDOI: 10.2210/pdb9g9x/pdb
• EMDBエントリー: 51160
• 分子名称: Potassium channel subfamily K member 3, CHOLESTEROL HEMISUCCINATE, POTASSIUM ION (3 entities in total)
• 機能のキーワード: k2p, membrane protein, potassium channel, ion channel
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62298.23

構造登録者

Rodstrom, K.E.J.,Hall, P.H.,Tucker, S.J. (登録日: 2024-07-25, 公開日: 2024-12-18, 最終更新日: 2025-01-15)

主引用文献

Hall, P.R.,Jouen-Tachoire, T.,Schewe, M.,Proks, P.,Baukrowitz, T.,Carpenter, E.P.,Newstead, S.,Rodstrom, K.E.J.,Tucker, S.J.
Structures of TASK-1 and TASK-3 K2P channels provide insight into their gating and dysfunction in disease.
Structure, 33:115-, 2025

PubMed Abstract: TASK-1 and TASK-3 are pH-sensitive two-pore domain (K2P/KCNK) K channels. Their functional roles make them promising targets for treatment of multiple disorders including sleep apnea, pain, and atrial fibrillation. Mutations in these channels are also associated with neurodevelopmental and hypertensive disorders. A previous crystal structure of TASK-1 revealed a lower "X-gate" as a hotspot for missense gain-of-function (GoF) mutations associated with DDSA (developmental delay with sleep apnea). However, the mechanisms of gating in TASK channels are still not fully understood. Here, we resolve structures for both human TASK-1 and TASK-3 by cryoelectron microscopy (cryo-EM), as well as a recurrent TASK-3 variant (G236R) associated with KCNK9 imprinting syndrome (KIS) (formerly known as Birk-Barel syndrome). Combined with functional studies of the X-gating mechanism, we provide evidence for how a highly conserved gating mechanism becomes defective in disease, and also provide further insight into the pathway of conformational changes that underlie the pH-dependent inhibition of TASK channel activity.

PubMed: 39637865
DOI: 10.1016/j.str.2024.11.005

実験手法

ELECTRON MICROSCOPY (3.13 Å)