Ion currents through Kir potassium channels are gated by anionic lipids.
Ion currents through Kir potassium channels are gated by anionic lipids.
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DOI：
10.1038/s41467-022-28148-4
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发表时间：
2022-01-25
影响因子：
16.6
通讯作者：
Gulbis JM
中科院分区：
文献类型：
--
作者：
Jin R;He S;Black KA;Clarke OB;Wu D;Bolla JR;Johnson P;Periasamy A;Wardak A;Czabotar P;Colman PM;Robinson CV;Laver D;Smith BJ;Gulbis JM
通过钾离子通道的离子电流是门控的。内部螺旋束的离子传导途径（Kir钾通道的教科书门）的收缩已被证明是一种无效的渗透控制，在我们对这些通道如何门控的理解中造成了裂缝。在这里，我们提出的证据表明，阴离子脂质作为相互作用的响应元件，足以门钾传导。我们证明了K+渗透的限制屏障位于离子传导途径内，并表明该门是由脂质的脂肪酰基尾部操作的，脂质通过孔壁上的开孔渗透到传导途径中。酰基尾部占据从细胞质界面延伸到传导途径的表面凹槽，提供了一种将细胞信号传递到内部通道的潜在手段，这种信号是由在典型脂质结合位点结合的阴离子脂质头基团介导的。已知Kir钾通道在没有主要构象变化的情况下运作和关闭。在这里，作者将Kir通道的渗透门确定为传导途径中的一个立体塞，描述了与之紧密相关的阴离子脂质如何推入孔壁的孔洞中，与塞接触以操作门。
Ion currents through potassium channels are gated. Constriction of the ion conduction pathway at the inner helix bundle, the textbook gate of Kir potassium channels, has been shown to be an ineffective permeation control, creating a rift in our understanding of how these channels are gated. Here we present evidence that anionic lipids act as interactive response elements sufficient to gate potassium conduction. We demonstrate the limiting barrier to K+ permeation lies within the ion conduction pathway and show that this gate is operated by the fatty acyl tails of lipids that infiltrate the conduction pathway via fenestrations in the walls of the pore. Acyl tails occupying a surface groove extending from the cytosolic interface to the conduction pathway provide a potential means of relaying cellular signals, mediated by anionic lipid head groups bound at the canonical lipid binding site, to the internal gate. The Kir potassium channels are known to operate and gate without a major conformational change. Here, the authors identify the permeation gate of Kir channels as a steric plug within the conduction pathway, describing how tightly associated anionic lipids pushing into fenestrations in the pore walls engage with the plug to operate the gate.
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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
影响因子：
14.8
作者：
Lichtenegger M;Tiapko O;Svobodova B;Stockner T;Glasnov TN;Schreibmayer W;Platzer D;de la Cruz GG;Krenn S;Schober R;Shrestha N;Schindl R;Romanin C;Groschner K
通讯作者：
Groschner K
TRIC 三聚体细胞内阳离子通道直系同源物的晶体结构。
影响因子：
44.1
作者：
通讯作者：
--
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.5
作者：
Hub, Jochen S.;de Groot, Bert L.;van der Spoel, David
通讯作者：
van der Spoel, David