6W82

K2P2.1 (TREK-1), 50 mM K+

6W82 の概要

• エントリーDOI: 10.2210/pdb6w82/pdb
• 関連するPDBエントリー: 6w7b 6w7c 6w7d 6w7e
• 分子名称: Potassium channel subfamily K member 2, CADMIUM ION, N-OCTANE, ... (9 entities in total)
• 機能のキーワード: ion channel, k2p, trek1, trek-1, metal transport
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70313.27

構造登録者

Lolicato, M.,Minor, D.L. (登録日: 2020-03-20, 公開日: 2021-01-27, 最終更新日: 2024-11-06)

主引用文献

Lolicato, M.,Natale, A.M.,Abderemane-Ali, F.,Crottes, D.,Capponi, S.,Duman, R.,Wagner, A.,Rosenberg, J.M.,Grabe, M.,Minor Jr., D.L.
K 2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.
Sci Adv, 6:-, 2020

PubMed Abstract: K potassium channels regulate cellular excitability using their selectivity filter (C-type) gate. C-type gating mechanisms, best characterized in homotetrameric potassium channels, remain controversial and are attributed to selectivity filter pinching, dilation, or subtle structural changes. The extent to which such mechanisms control C-type gating of innately heterodimeric Ks is unknown. Here, combining K2.1 (TREK-1) x-ray crystallography in different potassium concentrations, potassium anomalous scattering, molecular dynamics, and electrophysiology, we uncover unprecedented, asymmetric, potassium-dependent conformational changes that underlie K C-type gating. These asymmetric order-disorder transitions, enabled by the K heterodimeric architecture, encompass pinching and dilation, disrupt the S1 and S2 ion binding sites, require the uniquely long K SF2-M4 loop and conserved "M3 glutamate network," and are suppressed by the K C-type gate activator ML335. These findings demonstrate that two distinct C-type gating mechanisms can operate in one channel and underscore the SF2-M4 loop as a target for K channel modulator development.

PubMed: 33127683
DOI: 10.1126/sciadv.abc9174

実験手法

X-RAY DIFFRACTION (3.6 Å)