电压门式Na+/H+交换机的结构和机电合
Hyunku Yeo1, Ved Mehta1, Ashutosh Gulati1
1Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.
Nature
|October 25, 2023
概括
由电压感应域调节的精子输送器SLC9C1激活精子运动. 化电磁结构显示出其独特的电压激活机制, 对于受精至关重要.
科学领域:
- 结构生物学
- 分子和细胞生理学
- 生殖生物学
背景情况:
- 电压感应域 (VSD) 通常调节离子通道,但SLC9C1是一个独特的例外.
- 精子特异性SLC9C1对于精子运动和受精至关重要,它调解pH值变化和CatSper通道激活.
- SLC9C1电压激活的分子机制仍然难以捉摸.
研究的目的:
- 阐明精子Na+/H+交换器SLC9C1中电压依赖激活的结构基础.
- 了解VSD和循环核酸结合域在SLC9C1功能中的作用.
主要方法:
- 用冷电子显微镜 (cryo-EM) 确定海SLC9C1的结构.
- 在洗剂和纳米光盘中对SLC9C1的结构分析,有或没有cAMP.
主要成果:
- 新的冷EM结构显示出SLC9C1同位体旁边的异常VSD配置.
- 一个长的S4段将VSD连接到循环核酸结合域,采用非活跃的"上"形状.
- 细胞内螺旋在不活跃状态下限制离子运输,在超极化和cAMP结合时通过S4运动得到缓解.
结论:
- 这项研究揭示了SLC9C1中电压依赖的Na+/H+交换的结构机制.
- 由cAMP调节的超极化诱导的S4段运动是SLC9C1激活的关键.
- 这项研究提供了精子功能和受精过程的关键见解.
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