离子和脂质通道TMEM16F的结构异质性
Zhongjie Ye1,2, Nicola Galvanetto3,4, Leonardo Puppulin5,6
1International School for Advanced Studies (SISSA), 34136, Trieste, Italy.
Nature communications
|January 3, 2024
概括
跨膜蛋白16F (TMEM16F) 是一种离子通道和混杂酶,具有多样化的结构和机械特性. 离子激活会诱导逐步的孔隙变化,将形状异质性与其在离子和脂质运输中的功能联系起来.
科学领域:
- 生物物理学的生物物理.
- 结构生物学 结构生物学
- 膜蛋白质 膜蛋白质 膜蛋白质
背景情况:
- 跨膜蛋白16F (TMEM16F) 是一种Ca2+激活蛋白质,具有作为离子通道和脂 scramblase 的双重作用.
- 现有的冷电子显微镜 (cryo-EM) 结构提供有限的洞察力TMEM16F的激活机制和基板转位由于受限制的构造状态.
研究的目的:
- 在生理条件下研究TMEM16F的形状景观和机械特性.
- 阐明结构多样性在TMEM16F的离子通道和混杂酶功能中的作用.
主要方法:
- 在生理条件下的原子力显微镜 (AFM).
- 电生理学分析. 电生理学分析.
- 蛋白质结构异质性的分析.
主要成果:
- AFM揭示了多样化的TMEM16F组件,具有可变的子单元间接口和原质体方向,在以前的冷EM研究中没有观察到.
- 离子 (Ca2+) 激活诱导了孔区域的逐步变化,改变了TM3,TM4和TM6跨膜螺旋体的机械性质.
- 直接观察Ca2+诱导的膜重塑与脂质和离子透相关的结构多重性.
结论:
- 形态异质性是TMEM16F结构和功能的一个关键特征.
- TMEM16F的多种结构状态直接导致其在离子和脂质运输中的复杂生理作用.
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