Princess Margaret Cancer Centre; Department of Medical Biophysics; University of Toronto; Toronto, ON, Canada.
Channels (Austin). 2013 Sep-Oct;7(5):344-53. doi: 10.4161/chan.26734. Epub 2013 Nov 8.
Store-operated calcium (Ca(2+)) entry is the process by which molecules located on the endo/sarcoplasmic reticulum (ER/SR) respond to decreased luminal Ca(2+) levels by signaling Ca(2+) release activated Ca(2+) channels (CRAC) channels to open on the plasma membrane (PM). This activation of PM CRAC channels provides a sustained cytosolic Ca(2+) elevation associated with myriad physiological processes. The identities of the molecules which mediate SOCE include stromal interaction molecules (STIMs), functioning as the ER/SR luminal Ca(2+) sensors, and Orai proteins, forming the PM CRAC channels. This review examines the current available high-resolution structural information on these CRAC molecular components with particular focus on the solution structures of the luminal STIM Ca(2+) sensing domains, the crystal structures of cytosolic STIM fragments, a closed Orai hexameric crystal structure and a structure of an Orai1 N-terminal fragment in complex with calmodulin. The accessible structural data are discussed in terms of potential mechanisms of action and cohesiveness with functional observations.
钙库操纵性钙（Ca(2+)）内流是一种过程，内质网/肌浆网（ER/SR）上的分子通过信号转导，响应腔室内 Ca(2+)水平降低，从而打开质膜（PM）上的 Ca(2+)释放激活的 Ca(2+)通道（CRAC）。PM CRAC 通道的这种激活提供了与众多生理过程相关的持续细胞溶质 Ca(2+)升高。介导 SOCE 的分子包括基质相互作用分子（STIMs），作为 ER/SR 腔室 Ca(2+)传感器，以及 Orai 蛋白，形成 PM CRAC 通道。本综述检查了这些 CRAC 分子成分的当前可用高分辨率结构信息，特别关注腔室 STIM Ca(2+)感应结构域的溶液结构、细胞质 STIM 片段的晶体结构、封闭的 Orai 六聚体晶体结构以及与钙调蛋白结合的 Orai1 N 端片段的结构。可访问的结构数据根据潜在的作用机制和与功能观察的一致性进行了讨论。
