纳米盘中的TRPV1结构揭示了连接体和脂质作用的机制
Yuan Gao1,2, Erhu Cao1, David Julius1
1Department of Physiology, University of California, San Francisco, California 94143, USA.
Nature
|June 10, 2016
概括
使用冷EM和纳米磁盘研究大鼠TRPV1离子通道,发现了脂质相互作用. 特定的脂调节毒素结合,并可能通过取代素类分子来控制道激活.
科学领域:
- 结构生物学
- 生物物理
- 膜蛋白研究
背景情况:
- 在洗剂等人工系统中研究整体膜蛋白可以省略影响蛋白质结构和功能的关键脂质相互作用.
- 脂质在许多膜蛋白中起着重要的结构和调节作用,包括离子通道.
研究的目的:
- 在原生脂质双层环境中确定老鼠TRPV1离子通道的结构.
- 阐明特定脂质在TRPV1结构,功能和调节中的作用.
主要方法:
- 使用脂质纳米盘技术的结合电子冷显微镜 (cryo-EM).
- 在接近原生膜环境中可视化了老鼠TRPV1离子通道.
主要成果:
- 确定了TRPV1通道周围环状和调节性脂质的位置.
- 证明特定的脂相互作用增强了蜘蛛毒素与TRPV1的结合,形成了三方复合体.
- 发现酸丁脂占据了化物结合部位,这表明它在道激活中起着调节作用.
结论:
- 与冷EM结合的脂质纳米盘技术对于研究类似本地环境中的膜蛋白具有强大作用.
- 特定的脂质蛋白相互作用对TRPV1通道结构,毒素结合和全调节至关重要.
- 通过化学或热刺激激活TRPV1可能涉及调节性脂质从化物结合部位的移位.
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