在奥托佩林质子通道中,质子导电的结构机制
Ninghai Gan1,2, Weizhong Zeng1,2, Yan Han2
1Howard Hughes Medical Institute and Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature communications
|August 23, 2024
概括
奥托佩特林 (OTOP) 通道是质子通道. 这项研究揭示了OTOP8和OTOP2的构造变化,详细介绍了质子通路和通道活性调节机制.
科学领域:
- 生物物理学的生物物理.
- 结构生物学 结构生物学
- 分子生理学分子生理学
背景情况:
- 奥托佩林 (OTOP) 蛋白质作为细胞外质子激活的质子通道.
- 最近的结构显示OTOP通道形成双管架构的二极管.
- 关键的功能机制,包括pH激活和质子导电,仍然不清楚.
研究的目的:
- 在结构和功能上描述Caenorhabditis elegans OTOP8 (CeOTOP8) 和小鼠OTOP2 (mOTOP2).
- 阐明OTOP蛋白质中质子导电和通道门的基础构造变化.
主要方法:
- 进行X射线晶体学以确定CeOTOP8和mOTOP2.2的结构.
- 基于结构的突变发生,以调查特定残留物和运动的功能作用.
- 在CeOTOP8和mOTOP2.2之间进行比较结构分析.
主要成果:
- CeOTOP8结构揭示了N端TM12的形状变化,使得通过一个管间Glu/His桥实现过渡性质子转移.
- mOTOP2结构显示了N端的TM6形状变化,暴露了细胞外质素的中心谷氨酸.
- 在二次元接口上的子单位间运动对于调节OTOP通道活动至关重要.
结论:
- 提出了OTOP质子导电过程中的多步形状变化的详细工作模型.
- 对质子通道和门机制的结构洞察力为了解OTOP通道功能提供了基础.
- 这项研究阐明了细胞外pH感应和OTOP通道的质子传输的分子基础.
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