CRAC通道激活的连续步骤。
Sequential Steps of CRAC Channel Activation.
作者信息
Palty Raz, Fu Zhu, Isacoff Ehud Y
机构信息
Department of Biochemistry, Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
出版信息
Cell Rep. 2017 May 30;19(9):1929-1939. doi: 10.1016/j.celrep.2017.05.025.
Interaction between the endoplasmic reticulum protein STIM1 and the plasma membrane channel ORAI1 generates calcium signals that are central for diverse cellular functions. How STIM1 binds and activates ORAI1 remains poorly understood. Using electrophysiological, optical, and biochemical techniques, we examined the effects of mutations in the STIM1-ORAI1 activating region (SOAR) of STIM1. We find that SOAR mutants that are deficient in binding to resting ORAI1 channels are able to bind to and boost activation of partially activated ORAI1 channels. We further show that the STIM1 binding regions on ORAI1 undergo structural rearrangement during channel activation. The results suggest that activation of ORAI1 by SOAR occurs in multiple steps. In the first step, SOAR binds to ORAI1, partially activates the channel, and induces a rearrangement in the SOAR-binding site of ORAI1. That rearrangement of ORAI1 then permits sequential steps of SOAR binding, via distinct molecular interactions, to fully activate the channel.
内质网蛋白STIM1与质膜通道ORAI1之间的相互作用产生钙信号，这些信号对于多种细胞功能至关重要。STIM1如何结合并激活ORAI1仍知之甚少。我们使用电生理、光学和生化技术，研究了STIM1的STIM1-ORAI1激活区域（SOAR）中的突变效应。我们发现，与静息ORAI1通道结合存在缺陷的SOAR突变体能够结合并增强部分激活的ORAI1通道的激活。我们进一步表明，ORAI1上的STIM1结合区域在通道激活过程中会发生结构重排。结果表明，SOAR对ORAI1的激活分多个步骤进行。第一步，SOAR与ORAI1结合，部分激活通道，并诱导ORAI1的SOAR结合位点发生重排。然后，ORAI1的这种重排允许SOAR通过不同的分子相互作用依次结合步骤，以完全激活通道。
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