Structural and functional mechanisms of CRAC channel regulation.
Structural and functional mechanisms of CRAC channel regulation.
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DOI：
10.1016/j.jmb.2014.09.021
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发表时间：
2015-01-16
影响因子：
5.6
通讯作者：
Prakriya, Murali
中科院分区：
文献类型：
--
作者：
Shim, Ann Hye-Ryong;Tirado-Lee, Leidamarie;Prakriya, Murali
在许多动物细胞中，与G蛋白或酪氨酸激酶偶联的细胞表面受体的刺激通过钙库操纵的Ca 2+释放激活的Ca 2+（CRAC）通道动员Ca 2+内流。随后的Ca2+进入调节多种效应细胞反应，包括转录、运动和增殖。CRAC通道对人类健康的生理重要性通过研究强调，表明CRAC通道基因的突变产生一系列破坏性疾病，包括慢性炎症、肌无力和严重的联合免疫缺陷综合征。此外，从基础科学的角度来看，CRAC通道表现出独特的生物物理指纹，其特征是精致的Ca 2+选择性、储存操纵的门控和独特的孔隙特性，因此可以作为理解离子渗透和门控的生物物理机制的迷人离子通道。过去二十年的研究已经揭示了CRAC通道激活过程的细胞和分子编排，并且现在确定CRAC通道的打开通过孔形成奥赖蛋白和ER Ca 2+传感器STIM 1和STIM 2之间的直接相互作用来控制。在这篇综述中，我们总结了CRAC通道调控的功能和结构机制，重点介绍了我们对CRAC通道门控的构象和结构动力学的理解的最新进展。
In many animal cells, stimulation of cell surface receptors coupled to G proteins or tyrosine kinases mobilizes Ca2+ influx through store-operated Ca2+ release-activated Ca2+ (CRAC) channels. The ensuing Ca2+ entry regulates a wide variety of effector cell responses including transcription, motility, and proliferation. The physiological importance of CRAC channels for human health is underscored by studies indicating that mutations in CRAC channel genes produce a spectrum of devastating diseases including chronic inflammation, muscle weakness, and a severe combined immunodeficiency syndrome. Moreover, from a basic science perspective, CRAC channels exhibit a unique biophysical fingerprint characterized by exquisite Ca2+-selectivity, store-operated gating, and distinct pore properties and therefore serve as fascinating ion channels for understanding the biophysical mechanisms of ion permeation and gating. Studies in the last two decades have revealed the cellular and molecular choreography of the CRAC channel activation process, and it is now established that opening of CRAC channels is governed through direct interactions between the pore-forming Orai proteins, and the ER Ca2+ sensors, STIM1 and STIM2. In this review, we summarize the functional and structural mechanisms of CRAC channel regulation, focusing on recent advances in our understanding of the conformational and structural dynamics of CRAC channel gating.
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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：
HOTH, M;PENNER, R
通讯作者：
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DOI：
10.1073/pnas.0806499105
发表时间：
2008-09-09
影响因子：
11.1
作者：
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通讯作者：
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DOI：
10.1073/pnas.0608358103
发表时间：
2006-11-07
影响因子：
11.1
作者：
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通讯作者：
Kurosaki, Tomohiro
影响因子：
4.5
作者：
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通讯作者：
Feske, Stefan