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Cryo-EM structure of the zebrafish two pore domain K+ channel TREK1 (K2P2.1) in DDM/POPE mixed micellesCryo-EM structure of the zebrafish two pore domain K+ channel TREK1 (K2P2.1) in DDM/POPE mixed micelles
Structural highlights
FunctionPublication Abstract from PubMedTandem 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. Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1.,Schmidpeter PAM, Petroff JT 2nd, Khajoueinejad L, Wague A, Frankfater C, Cheng WWL, Nimigean CM, Riegelhaupt PM Nat Commun. 2023 Feb 25;14(1):1077. doi: 10.1038/s41467-023-36765-w. PMID:36841877[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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