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机械敏感 OSCA 通道的结构。

Structure of the mechanosensitive OSCA channels.

机构信息

State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Beijing, China.

Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.

出版信息

Nat Struct Mol Biol. 2018 Sep;25(9):850-858. doi: 10.1038/s41594-018-0117-6. Epub 2018 Sep 6.

Abstract

Mechanosensitive ion channels convert mechanical stimuli into a flow of ions. These channels are widely distributed from bacteria to higher plants and humans, and are involved in many crucial physiological processes. Here we show that two members of the OSCA protein family in Arabidopsis thaliana, namely AtOSCA1.1 and AtOSCA3.1, belong to a new class of mechanosensitive ion channels. We solve the structure of the AtOSCA1.1 channel at 3.5-Å resolution and AtOSCA3.1 at 4.8-Å resolution by cryo-electron microscopy. OSCA channels are symmetric dimers that are mediated by cytosolic inter-subunit interactions. Strikingly, they have structural similarity to the mammalian TMEM16 family proteins. Our structural analysis accompanied with electrophysiological studies identifies the ion permeation pathway within each subunit and suggests a conformational change model for activation.

摘要

机械敏感离子通道将机械刺激转化为离子流。这些通道广泛存在于从细菌到高等植物和人类的生物体中,并参与许多关键的生理过程。在这里,我们展示了拟南芥中 OSCA 蛋白家族的两个成员,即 AtOSCA1.1 和 AtOSCA3.1,属于一类新型的机械敏感离子通道。我们通过冷冻电镜解析了 AtOSCA1.1 通道的结构,分辨率为 3.5-Å,AtOSCA3.1 通道的结构分辨率为 4.8-Å。OSCA 通道是由细胞质亚基间相互作用介导的对称二聚体。引人注目的是,它们与哺乳动物 TMEM16 家族蛋白具有结构相似性。我们的结构分析结合电生理研究确定了每个亚基内的离子渗透途径,并提出了一种激活的构象变化模型。

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