Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation.
Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation.
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DOI：
10.1038/s41467-022-34813-5
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发表时间：
2022-11-17
影响因子：
16.6
通讯作者：
Cheng, Wayland W. L.
中科院分区：
文献类型：
--
作者：
Petroff, John T.;Dietzen, Noah M.;Santiago-McRae, Ezry;Deng, Brett;Washington, Maya S.;Chen, Lawrence J.;Moreland, K. Trent;Deng, Zengqin;Rau, Michael;Fitzpatrick, James A. J.;Yuan, Peng;Joseph, Thomas T.;Henin, Jerome;Brannigan, Grace;Cheng, Wayland W. L.
五聚体配体门控离子通道 (pLGIC) 介导突触传递并对脂质环境敏感。任何 pLGIC 的磷脂调节机制尚不清楚。我们证明模型 pLGIC、ELIC（欧文氏菌配体门控离子通道）受到来自膜外层的阴离子磷脂、磷脂酰甘油的正向调节。为了探索磷脂酰甘油调节的机制，我们确定了 ELIC 的开放通道构象结构。该结构显示了外叶位点中的结合磷脂，以及开放通道特有的磷脂结合位点的结构变化。结合简化的炼金术自由能微扰计算和不对称脂质体的功能测量，这些数据支持阴离子磷脂通过与该位点特异性、状态依赖性结合来稳定 pLGIC 的激活、开放通道状态的机制。五聚体配体门控离子通道由阴离子磷脂调节。在这里，通过捕获 ELIC 的开放通道构象，作者展示了通道激活的结构细节以及磷脂酰甘油调节的小叶特异性机制。
Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation of any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinia ligand-gated ion channel), is positively modulated by the anionic phospholipid, phosphatidylglycerol, from the outer leaflet of the membrane. To explore the mechanism of phosphatidylglycerol modulation, we determine a structure of ELIC in an open-channel conformation. The structure shows a bound phospholipid in an outer leaflet site, and structural changes in the phospholipid binding site unique to the open-channel. In combination with streamlined alchemical free energy perturbation calculations and functional measurements in asymmetric liposomes, the data support a mechanism by which an anionic phospholipid stabilizes the activated, open-channel state of a pLGIC by specific, state-dependent binding to this site. Pentameric ligand-gated ion channels are modulated by anionic phospholipids. Here, by capturing an open-channel conformation of ELIC, the authors demonstrate the structural details of channel activation and a leaflet-specific mechanism for modulation by phosphatidylglycerol.
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影响因子：
4.3
作者：
Dämgen MA;Biggin PC
通讯作者：
Biggin PC
影响因子：
2.9
作者：
CRIADO, M;EIBL, H;BARRANTES, FJ
通讯作者：
BARRANTES, FJ
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
7.7
作者：
Dietzen NM;Arcario MJ;Chen LJ;Petroff JT 2nd;Moreland KT;Krishnan K;Brannigan G;Covey DF;Cheng WW
通讯作者：
Cheng WW
影响因子：
4.8
作者：
daCosta, Corrie J. B.;Baenziger, John E.
通讯作者：
Baenziger, John E.