8DE8

Cryo-EM structure of the zebrafish two pore domain K+ channel TREK1 (K2P2.1) in DDM/POPA mixed micelles

8DE8 の概要

• エントリーDOI: 10.2210/pdb8de8/pdb
• EMDBエントリー: 27387
• 分子名称: Potassium channel, subfamily K, member 2a, (2R)-1-(hexadecanoyloxy)-3-(phosphonooxy)propan-2-yl (9Z)-octadec-9-enoate, POTASSIUM ION (3 entities in total)
• 機能のキーワード: ion channel, k2p, k2p2.1, trek1, trek-1, popa, membrane protein
• 由来する生物種: Danio rerio (zebrafish)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73974.87

構造登録者

Schmidpeter, P.A.M.,Nimigean, C.M.,Riegelhaupt, P.M. (登録日: 2022-06-20, 公開日: 2023-03-08, 最終更新日: 2024-10-09)

主引用文献

Schmidpeter, P.A.M.,Petroff 2nd, J.T.,Khajoueinejad, L.,Wague, A.,Frankfater, C.,Cheng, W.W.L.,Nimigean, C.M.,Riegelhaupt, P.M.
Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1.
Nat Commun, 14:1077-1077, 2023

PubMed Abstract: Tandem pore domain (K2P) potassium channels modulate resting membrane potentials and shape cellular excitability. For the mechanosensitive subfamily of K2Ps, the composition of phospholipids within the bilayer strongly influences channel activity. To examine the molecular details of K2P lipid modulation, we solved cryo-EM structures of the TREK1 K2P channel bound to either the anionic lipid phosphatidic acid (PA) or the zwitterionic lipid phosphatidylethanolamine (PE). At the extracellular face of TREK1, a PA lipid inserts its hydrocarbon tail into a pocket behind the selectivity filter, causing a structural rearrangement that recapitulates mutations and pharmacology known to activate TREK1. At the cytoplasmic face, PA and PE lipids compete to modulate the conformation of the TREK1 TM4 gating helix. Our findings demonstrate two distinct pathways by which anionic lipids enhance TREK1 activity and provide a framework for a model that integrates lipid gating with the effects of other mechanosensitive K2P modulators.

PubMed: 36841877
DOI: 10.1038/s41467-023-36765-w

実験手法

ELECTRON MICROSCOPY (2.82 Å)