对LRRC8体积调节的离子通道的离子选择性和激活机制的结构性见解
Heng Liu1, Maya M Polovitskaya2, Linlin Yang3
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Cell reports
|August 6, 2023
概括
量调节的离子通道 (VRACs) 使用N termini (NTs) 来控制离子流和选择性. 细胞胀改变了NT的流动性,这表明了VRAC激活的新机制.
科学领域:
- 结构生物学是结构生物学.
- 分子生物物理学的分子生物物理学.
- 细胞生理细胞生理学
背景情况:
- 体积调节的离子通道 (VRACs) 对于细胞体积恒温至关重要.
- LRRC8A子单元的N端 (NT) 是已知的VRAC功能的调节器,但它们的结构作用尚不清楚.
研究的目的:
- 阐明LRRC8A N termini调节VRAC离子选择性和激活的结构机制.
- 研究NTs在通道架构和对离子强度的反应中的作用.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定人类LRRC8A的高分辨率结构.
- 分子动力学 (MD) 模拟用于分析不同离子条件下的通道行为.
主要成果:
- 一个2.8 Å的冷-EM结构显示了高分辨率的LRRC8A N termini.
- NTs的氨基末端半端形成细胞内收缩,与细胞外的序列作为选择性过器.
- NTs的C端半端与细胞内循环相互作用,影响道激活.
结论:
- LRRC8A NTs有助于一个独特的,双过孔结构.
- 离子强度的变化影响了NT的移动性和通道门,为细胞胀的VRAC激活提供了洞察力.
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