由ER耗竭激活STIM1的基础上的结构重组
bioRxiv : the preprint server for biology
|February 6, 2026
概括
从STIM1 (Stromal Interaction Molecule 1) 中释放的 (Ca2+) 触发了结构变化,通过一种新的折叠机制释放了CRAC激活域 (CAD). 这种重新排列对于激活Orai1通道和储存运行的入口 (SOCE) 至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 流体相互作用分子1 (STIM1) 在内分泌网膜 (ER) 中充当 (Ca2+) 传感器.
- 通过调节Orai1通道,STIM1控制了储存运行的进入 (SOCE).
- 在静止细胞中,STIM1通过分子内限制保持不活跃.
研究的目的:
- 阐明由STIM1释放的Ca2+驱动其细胞质域的结构变化的机制.
- 了解如何释放CRAC激活域 (CAD) 来激活Orai1通道.
主要方法:
- 单分子弗斯特尔共振能量转移 (smFRET) 测量.
- 使用了纯化的STIM1蛋白.
- 采用氨酸交叉链接来探测结构重组.
主要成果:
- 从STIM1中去除Ca2+释放了CC1的CAD,而没有强制性的CC1卷轴-卷轴形成.
- 在释放过程中,CAD经历了戏剧性的重新排列,使其质体在释放过程中分散.
- 锁定CAD原体在一起的氨酸交叉连接阻止了CAD释放,表明重新排列是必不可少的.
结论:
- 提出了一个模型,其中ER Ca2+耗尽诱导STIM1光SAM域二元化.
- 这种二度化稳定了一个中间结构,释放了CC1.
- 该CAD通过"折叠"机制逃逸,随后恢复到其积极的构造以打开Orai1通道.
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