对STIM1介导的商店运营入口启动的结构和机制见解
Peter B Stathopulos1, Le Zheng, Guang-Yao Li
1Division of Signaling Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto Medical Discovery Tower, MaRS Centre, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
Cell
|October 16, 2008
概括
流体相互作用分子-1 (STIM1) 调节的进入. 它的Ca2+感应EF-SAM区域
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 流体相互作用分子-1 (STIM1) 是储存运行的进入 (SOCE) 的关键调节器.
- STIM1激活是由细胞内储存的水平降低所触发的.
研究的目的:
- 为了确定STIM1 Ca2+感应EF-SAM区域的原子结构.
- 阐明STIM1介导的SOCE启动背后的分子机制.
主要方法:
- 进行X射线晶体学以确定STIM1 EF-SAM域的原子结构.
- 局部定向突变发生,以调查特定残留物和域的作用.
- 在哺乳动物细胞中进行基于细胞的测试,以评估STIM1功能和SOCE活性.
主要成果:
- STIM1 EF-SAM区域的原子结构揭示了与SAM域相互作用的双 EF 手动图.
- 破坏EF手或SAM域相互作用的突变破坏了EF-SAM实体的稳定性,影响了Ca2+敏感性和寡合化.
- 在全长STIM1诱导的点形成和细胞中Ca2+独立的SOCE激活中的破坏稳定性突变.
结论:
- STIM1 EF-SAM区域的折叠/展开状态对于调节SOCE至关重要.
- 原子水平的结构洞察力解释了STIM1介导的SOCE启动的分子基础.
- EF-手对和SAM域相互作用对STIM1的Ca2+敏感性和功能至关重要.
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