一个带有扩张孔的米TRPV3通道
Shifra Lansky1, John Michael Betancourt1,2, Jingying Zhang3,4,5
1Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA.
Nature
|August 30, 2023
概括
研究人员使用高速原子力显微镜在TRPV3通道中发现了一个非正规的形状态. 这种与四度体的动态平衡中观察到的五度体组合与孔隙扩张相关,并为TRP通道结构提供了新的见解.
科学领域:
- 结构生物学
- 离子通道生物物理
- 分子生理学
背景情况:
- 短暂受体潜能 (TRP) 道是具有不同生理作用的关键真核离子道超级家族,使其成为重要的药物标.
- 虽然存在众多的TRP通道结构,但TRPV通道孔扩张的机制,其特点是电导率和透性增加,仍然不太清楚.
- 已知正规的TRP通道结构为四重体.
研究的目的:
- 在单个分子水平上研究TRPV3通道孔隙扩张的结构基础.
- 探索TRP通道的潜在非正规结构组合,超出已建立的四重体形式.
主要方法:
- 高速原子力显微镜 (HS-AFM) 用于嵌入膜TRPV3的动态单分子成像.
- 用冷电子显微镜 (冷电子显微镜) 确定TRPV3组件的高分辨率结构.
- 使用专门的蛋白质生产和数据分析管道.
主要成果:
- 发现TRPV3通道与正规四度体处于动态平衡的短暂和可逆的度状态.
- 在添加基化物 (DPBA) 时增加体形成,这是一种已知的诱导孔隙扩张的激动剂.
- 与四度体相比,冷-EM结构显示了五度体状态中的孔径扩大,与孔径扩大相关.
结论:
- 体TRPV3组件代表了孔隙扩张现象的结构相关性.
- 膜扩散原体交换被认为是TRP通道结构变化和构造变化的机制.
- 提供了非规范性米TRP通道组件的第一个结构证据,为TRP通道研究开辟了新的途径.
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