The STIM1-binding site nexus remotely controls Orai1 channel gating.
The STIM1-binding site nexus remotely controls Orai1 channel gating.
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STIM1结合位点Nexus远程控制ORAI1通道门控。
DOI：
10.1038/ncomms13725
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发表时间：
2016-12-08
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
普遍表达的奥赖Ca 2+通道通过与Ca 2+敏感STIM蛋白的膜间偶联的独特过程被门控。尽管Orai 1介导的Ca 2+信号的重要性，但STIM 1如何触发Orai 1的门控仍然未知。一个广泛持有的门控模型调用STIM 1直接结合到Orai 1孔形成螺旋。在这里，我们报告说，Orai 1 C-末端STIM 1结合位点，位于远离N-末端孔螺旋，单独提供的触发器，是必要的和足够的通道门控。我们确定了Orai 1内连接外围C-末端STIM 1结合位点到Orai 1核心螺旋的关键“连接”。连接的突变将Orai 1转变为持续开放状态，完全模仿STIM 1的作用。我们认为Orai 1连接通过内核螺旋中的构象变化转导STIM 1结合信号，并且STIM 1远程门控Orai 1通道，而不需要STIM 1与成孔螺旋直接接触。 质膜奥赖Ca 2+通道如何被STIM蛋白激活以激活Ca 2+信号仍然不完全清楚。在这里，作者表明，位于Orai 1 C末端的连接区域允许通道门控，而无需STIM 1与通道孔的直接相互作用。
The ubiquitously expressed Orai Ca2+ channels are gated through a unique process of intermembrane coupling with the Ca2+-sensing STIM proteins. Despite the significance of Orai1-mediated Ca2+ signals, how gating of Orai1 is triggered by STIM1 remains unknown. A widely held gating model invokes STIM1 binding directly to Orai1 pore-forming helix. Here we report that an Orai1 C-terminal STIM1-binding site, situated far from the N-terminal pore helix, alone provides the trigger that is necessary and sufficient for channel gating. We identify a critical ‘nexus' within Orai1 connecting the peripheral C-terminal STIM1-binding site to the Orai1 core helices. Mutation of the nexus transforms Orai1 into a persistently open state exactly mimicking the action of STIM1. We suggest that the Orai1 nexus transduces the STIM1-binding signal through a conformational change in the inner core helices, and that STIM1 remotely gates the Orai1 channel without the necessity for direct STIM1 contact with the pore-forming helix. How plasma membrane Orai Ca2+ channels are activated by STIM proteins to activate Ca2+ signals is still not fully known. Here the authors show that a nexus region located at the Orai1 C-terminus allows channel gating without a direct interaction of STIM1 with the channel pore.
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影响因子：
64.5
作者：
Park CY;Hoover PJ;Mullins FM;Bachhawat P;Covington ED;Raunser S;Walz T;Garcia KC;Dolmetsch RE;Lewis RS
通讯作者：
Lewis RS
影响因子：
4
作者：
Hendron E;Wang X;Zhou Y;Cai X;Goto J;Mikoshiba K;Baba Y;Kurosaki T;Wang Y;Gill DL
通讯作者：
Gill DL
DOI：
10.1126/science.1228757
发表时间：
2012-12-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou X;Pedi L;Diver MM;Long SB
通讯作者：
Long SB
影响因子：
64.8
作者：
McNally, Beth A.;Somasundaram, Agila;Yamashita, Megumi;Prakriya, Murali
通讯作者：
Prakriya, Murali
影响因子：
5.5
作者：
McNally, Beth A.;Somasundaram, Agila;Prakriya, Murali
通讯作者：
Prakriya, Murali