Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1.
Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1.
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DOI：
10.1038/s41467-023-36765-w
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发表时间：
2023-02-25
影响因子：
16.6
通讯作者：
Riegelhaupt, Paul M.
中科院分区：
文献类型：
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作者：
Schmidpeter, Philipp A. M.;Petroff, John T.;Khajoueinejad, Leila;Wague, Aboubacar;Frankfater, Cheryl;Cheng, Wayland W. L.;Nimigean, Crina M.;Riegelhaupt, Paul M.
串联孔结构域(K2P)钾通道调节静息膜电位，形成细胞兴奋性。对于机械敏感的K2Ps亚家族，双层内磷脂的组成强烈影响通道活性。为了研究K2P调节脂质的分子细节，我们解决了TREK1 K2P通道与阴离子脂质磷脂酸(PA)或两性离子脂质磷脂酰乙醇胺(PE)结合的冷冻EM结构。在TREK1的胞外面，PA脂质将其碳氢化合物尾巴插入选择性过滤器后面的口袋中，导致结构重排，重述已知的激活TREK1的突变和药理。在细胞质表面，PA和PE脂类竞争调节TREK1 TM4门控螺旋的构象。我们的发现表明，阴离子脂类通过两种不同的途径增强TREK1的活性，并为将脂质门控与其他机械敏感性K2P调节剂的影响相结合的模型提供了一个框架。串联孔(K2P)钾通道在全身各组织中设定细胞静息膜电位。在这里，作者展示了双层内磷脂的组成如何直接改变这一家族离子通道的门控。
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. Tandem pore (K2P) potassium channels set the cellular resting membrane potential in tissues throughout the body. Here, authors show how the composition of phospholipid within the bilayer may directly alter gating in this family of ion channels.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
DOI：
10.1016/j.str.2017.03.006
发表时间：
2017-05-02
期刊：
Structure (London, England : 1993)
影响因子：
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作者：
Aryal P;Jarerattanachat V;Clausen MV;Schewe M;McClenaghan C;Argent L;Conrad LJ;Dong YY;Pike ACW;Carpenter EP;Baukrowitz T;Sansom MSP;Tucker SJ
通讯作者：
Tucker SJ
DOI：
10.1073/pnas.1407160111
发表时间：
2014-09-16
影响因子：
11.1
作者：
Comoglio, Yannick;Levitz, Joshua;Sandoz, Guillaume
通讯作者：
Sandoz, Guillaume
影响因子：
16.6
作者：
Ben Soussia, Ismail;El Mouridi, Sonia;Boulin, Thomas
通讯作者：
Boulin, Thomas
影响因子：
64.8
作者：
通讯作者：
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