STIM 和 Orai 结构特征与钙库操纵性钙内流。
Structural features of STIM and Orai underlying store-operated calcium entry.
机构信息
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States.
出版信息
Curr Opin Cell Biol. 2019 Apr;57:90-98. doi: 10.1016/j.ceb.2018.12.012. Epub 2019 Feb 1.
Abstract
Store-operated calcium entry (SOCE) through Orai channels is triggered by receptor-stimulated depletion of Ca from the ER. Orai1 is unique in terms of its activation mechanism, biophysical properties, and structure, and its precise regulation is essential for human health. Recent studies have begun to reveal the structural basis of the major steps in the SOCE pathway and how the system is reliably suppressed in resting cells but able to respond robustly to ER Ca depletion. In this review, we discuss current models describing the activation of ER Ca sensor STIM1, its binding to Orai1, propagation of the binding signal from the channel periphery to the central pore, and the resulting conformational changes underlying opening of the highly Ca selective Orai1 channel.
摘要
钙库操纵性钙内流（SOCE）通过 Orai 通道触发，该通道由受体刺激内质网（ER）中 Ca 耗竭引发。Orai1 的激活机制、生物物理特性和结构具有独特性，其精确调控对人类健康至关重要。最近的研究开始揭示 SOCE 途径的主要步骤的结构基础，以及该系统如何在静止细胞中被可靠地抑制，但能够对 ER Ca 耗竭做出强烈反应。在这篇综述中，我们讨论了目前描述 ER Ca 传感器 STIM1 激活、其与 Orai1 结合、结合信号从通道边缘向中央孔传播以及由此产生的高 Ca 选择性 Orai1 通道开放的构象变化的模型。
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