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结构引导的OSCA突变发生揭示了对机械刺激的差异激活

Sebastian Jojoa-Cruz¹, Adrienne E Dubin², Wen-Hsin Lee¹

¹Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, California 92037, USA.

bioRxiv : the preprint server for biology

|October 24, 2023

概括

在OSCA/TMEM63家族中的机械激活离子通道对膜拉伸与刺入的反应不同. 特定的结构元素,包括两螺旋,调解点击反应,有助于功能多样性.

科学领域:

分子生物学分子生物学
生物物理学的生物物理.
结构生物学结构生物学

背景情况:

OSCA/TMEM63家族包括二维的两孔机械激活离子通道.
这些通道是由膜张力激活的,但是不同的块对不同的机械刺激,如拉伸和刺入,表现出不同的反应.
了解这种功能多样性的结构基础至关重要.

研究的目的:

阐明在OSCA通道中负责机械信号传导的结构域.
研究OSCA3.1和OSCA1.2.2.中的拉伸激活电流和动激活电流之间的功能差异.
了解OSCA/TMEM63家族内功能多样性的分子基础.

主要方法:

低温电子显微镜测定Arabidopsis thaliana的结构 OSCA3.1.1.
在OSCA1.2.2.中的保留和分离的假定机械敏感特征的位点定向突变发生.
电生理学记录 (细胞附着的贴片) 用于通过伸展和刺穿来评估通道激活.

主要成果:

这项研究确定了Arabidopsis thaliana* OSCA3.1.1.的冷-EM结构.
OSCA1.2的突变性选择性地破坏了点击激活电流,同时在很大程度上保留了拉伸激活电流 (SAC).
膜化中的两螺旋和脂质相互作用的残留物与刺入的反应有关.

结论:

两螺旋和脂质相互作用的残留物是OSCA通道中刺激激活机制的关键贡献者.
这些结构元素可能解释了在OSCA/TMEM63家族中观察到的功能多样性.
研究结果提供了关于离子通道中机械感应的分子机制的见解.

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