Orai channel pore properties and gating by STIM: implications from the Orai crystal structure.
Orai channel pore properties and gating by STIM: implications from the Orai crystal structure.
复制标题
Orai通道孔特性和刺激门控：来自Orai晶体结构的含义。
DOI：
10.1126/scisignal.2003971
复制
发表时间：
2013-03-19
影响因子：
7.3
通讯作者：
Gill DL
中科院分区：
文献类型：
--
作者：
Rothberg BS;Wang Y;Gill DL
在大多数细胞类型中，奥赖通道是不寻常的，但突出的钙（Ca 2+）信号介质。奥赖蛋白在结构上是独特的，与其它离子通道具有很少的序列同源性。它们在功能上也是独特的，对Ca 2+具有极高的选择性，介导对转录控制重要的短期Ca 2+稳态和长期Ca 2+信号。奥赖通道在质膜（PM）中运行，其调节在离子通道中是前所未有的;通道门控通过与内质网（ER）中的基质相互作用分子（STIM）蛋白的精细膜间偶联发生。STIM蛋白作为储存在ER腔中的Ca 2+的传感器起作用，并且当ER Ca 2+浓度降低时，STIM蛋白移位到ER-PM连接处以束缚并激活奥赖通道。结晶研究揭示了一个意想不到的六聚体结构的奥赖通道，并提供了重要的见解的孔结构，其不寻常的阳离子选择性的结构基础，以及如何通过其耦合与STIM蛋白的通道门控发生。
The Orai channels are unusual, yet prominent, calcium (Ca2+) signal mediators in most cell types. Orai proteins are structurally unique, having little sequence homology with other ion channels. They are also functionally unique with exceedingly high selectivity for Ca2+, mediating both short-term Ca2+ homeostasis and long-term Ca2+ signals important for transcriptional control. Operating in the plasma membrane (PM), Orai channel regulation is unprecedented among ion channels; channel gating occurs through an elaborate intermembrane coupling with stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER). STIM proteins function as sensors of Ca2+ stored in the ER lumen and translocate into ER-PM junctions to tether and activate Orai channels when ER Ca2+ concentration decreases. Crystallization studies reveal an unexpected hexameric structure for the Orai channel and provide important insights into the pore architecture, the structural basis of its unusual cation selectivity, and how channel gating occurs through its coupling with STIM proteins.