- EMDB-36799: Human TWIK-related acid-sensitive potassium channel TASK3 at pH 6... -
+
データを開く
IDまたはキーワード:
読み込み中...
-
基本情報
登録情報
データベース: EMDB / ID: EMD-36799
タイトル
Human TWIK-related acid-sensitive potassium channel TASK3 at pH 6.0, 5 mM KCl and 135 mM NaCl
マップデータ
試料
複合体: CHS
タンパク質・ペプチド: Potassium channel subfamily K member 9
リガンド: CHOLESTEROL HEMISUCCINATE
リガンド: POTASSIUM ION
リガンド: water
キーワード
Acid-sensitive / potassium ion channel / C-type / gating mechanism / MEMBRANE PROTEIN
機能・相同性
機能・相同性情報
TWIK-releated acid-sensitive K+ channel (TASK) / Phase 4 - resting membrane potential / stabilization of membrane potential / potassium ion leak channel activity / outward rectifier potassium channel activity / potassium ion import across plasma membrane / potassium channel activity / potassium ion transmembrane transport / potassium ion transport / synaptic vesicle / plasma membrane 類似検索 - 分子機能
Potassium channel subfamily K member 9 / Two pore domain potassium channel, TASK family / Two pore domain potassium channel / Potassium channel domain / Ion channel 類似検索 - ドメイン・相同性
Potassium channel subfamily K member 9 類似検索 - 構成要素
National Natural Science Foundation of China (NSFC)
32301002
中国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2024 タイトル: C-type inactivation and proton modulation mechanisms of the TASK3 channel. 著者: Huajian Lin / Junnan Li / Qiansen Zhang / Huaiyu Yang / Shanshuang Chen / 要旨: The TWIK-related acid-sensitive K channel 3 (TASK3) belongs to the two-pore domain (K2P) potassium channel family, which regulates cell excitability by mediating a constitutive "leak" potassium ...The TWIK-related acid-sensitive K channel 3 (TASK3) belongs to the two-pore domain (K2P) potassium channel family, which regulates cell excitability by mediating a constitutive "leak" potassium efflux in the nervous system. Extracellular acidification inhibits TASK3 channel, but the molecular mechanism by which channel inactivation is coupled to pH decrease remains unclear. Here, we report the cryo-electron microscopy structures of human TASK3 at neutral and acidic pH. Structural comparison revealed selectivity filter (SF) rearrangements upon acidification, characteristic of C-type inactivation, but with a unique structural basis. The extracellular mouth of the SF was prominently dilated and simultaneously blocked by a hydrophobic gate. His98 protonation shifted the conformational equilibrium between the conductive and C-type inactivated SF toward the latter by engaging a cation-π interaction with Trp78, consistent with molecular dynamics simulations and electrophysiological experiments. Our work illustrated how TASK3 is gated in response to extracellular pH change and implies how physiological stimuli might directly modulate the C-type gating of K2P channels.