机械激活在OSCA离子通道中打开脂质层孔
Yaoyao Han1,2, Zijing Zhou3,4, Ruitao Jin5
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
机械敏感的OSCA/TMEM63通道使用独特的蛋白质脂质孔,脂质调节它们的门. 结构显示独立的子单元开放和跨OSCA道的保存机制.
科学领域:
- 生物物理
- 结构生物学
- 分子生物学
背景情况:
- OSCA/TMEM63通道构成最大的机械敏感离子通道家族.
- 这些通道对于植物和哺乳动物的机械传导至关重要.
- 了解它们的关门机制是细胞机械感知的关键.
研究的目的:
- 调查OSCA/TMEM63通道机械敏感性的分子基础.
- 在各种膜环境中确定OSCA/TMEM63通道的结构.
- 阐明脂质在道关中的作用.
主要方法:
- 低温电子显微镜 (cryo-EM) 来确定44个通道结构.
- 脂质体和纳米盘复合以模仿细胞膜条件.
- 功能测试和计算建模以支持结构发现.
主要成果:
- 在纳米磁盘中模拟膜张力下观察到扩张的毛孔.
- 捕获的完全开放的OSCA1.2结构与侧面的膜开口.
- 确定了一个"蛋白脂孔",脂质形成了离子透通道.
- 在OSCA3.1中发现了一种"相互锁定"的脂质,可以抑制道的开放.
- 证明突变的脂质协调残留物可以激活OSCA3.1.
结论:
- 提供了OSCA道封锁周期的全面视图.
- 突出结合脂质在道功能调节中的关键作用.
- 表明单个子单元可以独立打开,扩展机械传导知识.
- 提供了与TMEM16和TMC蛋白家族相关的机制性见解.
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