Calcium sensing by the STIM1 ER-luminal domain.
Calcium sensing by the STIM1 ER-luminal domain.
复制标题
STIM1 ER 腔域的钙感应。
DOI：
10.1038/s41467-018-06816-8
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发表时间：
2018-10-31
影响因子：
16.6
通讯作者：
Hogan PG
中科院分区：
文献类型：
--
作者：
Gudlur A;Zeraik AE;Hirve N;Rajanikanth V;Bobkov AA;Ma G;Zheng S;Wang Y;Zhou Y;Komives EA;Hogan PG
基质相互作用分子1（Stromal interaction molecule 1，STIM 1）监测ER-管腔Ca 2+水平以维持细胞Ca 2+平衡并支持Ca 2+信号传导。流行的观点是，STIM 1通过从单个EF-手位点解离结合的Ca 2+来感测减少的ER Ca 2+，这触发了STIM 1管腔结构域的二级结构和二聚化的显著损失。在这里，我们发现，STIM 1管腔域有5-6个Ca 2+结合位点，在这些位点的结合是积极耦合到EF-手网站的结合，和Ca 2+解离控制开关的第二个结构化构象的管腔域，而不是蛋白质展开。重要的是，其他腔域Ca 2+结合位点与EF-手位点相互作用，以控制细胞中STIM 1的生理激活。这些发现从根本上修订了我们对STIM 1生理Ca 2+传感的理解，并突出了控制激活的Ca 2+阈值和陡峭的Ca 2+浓度依赖性的分子机制。基质相互作用分子1（Stromal interaction molecule 1，STIM 1）监测ER-管腔Ca 2+水平以维持细胞Ca 2+平衡。在这里，作者发现STIM 1管腔结构域单体具有多个Ca 2+结合位点，这些位点为细胞中STIM 1的生理激活设定了阈值。
Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca2+ levels to maintain cellular Ca2+ balance and to support Ca2+ signalling. The prevailing view has been that STIM1 senses reduced ER Ca2+ through dissociation of bound Ca2+ from a single EF-hand site, which triggers a dramatic loss of secondary structure and dimerization of the STIM1 luminal domain. Here we find that the STIM1 luminal domain has 5–6 Ca2+-binding sites, that binding at these sites is energetically coupled to binding at the EF-hand site, and that Ca2+ dissociation controls a switch to a second structured conformation of the luminal domain rather than protein unfolding. Importantly, the other luminal-domain Ca2+-binding sites interact with the EF-hand site to control physiological activation of STIM1 in cells. These findings fundamentally revise our understanding of physiological Ca2+ sensing by STIM1, and highlight molecular mechanisms that govern the Ca2+ threshold for activation and the steep Ca2+ concentration dependence. Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca2+ levels to maintain cellular Ca2+ balance. Here the authors find that the STIM1 luminal domain monomer has multiple Ca2+ - binding sites which set the threshold for physiological activation of STIM1 in cells.
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影响因子：
64.5
作者：
Park CY;Hoover PJ;Mullins FM;Bachhawat P;Covington ED;Raunser S;Walz T;Garcia KC;Dolmetsch RE;Lewis RS
通讯作者：
Lewis RS
影响因子：
4.8
作者：
Mercer, Jason C.;DeHaven, Wayne I.;Putney, James W., Jr.
通讯作者：
Putney, James W., Jr.
影响因子：
2.9
作者：
EDELHOCH, H
通讯作者：
EDELHOCH, H
影响因子：
2.9
作者：
Le VH;Buscaglia R;Chaires JB;Lewis EA
通讯作者：
Lewis EA
影响因子：
7.3
作者：
Korzeniowski MK;Manjarrés IM;Varnai P;Balla T
通讯作者：
Balla T