Structure of the mechanically activated ion channel Piezo1.
Structure of the mechanically activated ion channel Piezo1.
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DOI：
10.1038/nature25453
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发表时间：
2018-02-22
期刊：
影响因子：
64.8
通讯作者：
Ward AB
中科院分区：
文献类型：
--
作者：
Saotome K;Murthy SE;Kefauver JM;Whitwam T;Patapoutian A;Ward AB
Piezo1和Piezo2是机械激活的离子通道，介导触觉感知、本体感觉和血管发育。压电离子通道不同于其他离子通道，其结构仍然不明确，阻碍了对其门控和离子渗透特性的详细研究。在这里，我们报告了小鼠Piezo1三聚体的高分辨率低温电子显微镜结构。该洗涤剂增溶配合物采用三叶片螺旋桨形状，其弯曲的跨膜区域包含每个原聚体至少26个跨膜螺旋。柔性螺旋桨叶片可以采用不同的构象，由一系列四跨膜螺旋束组成，我们称之为“压电重复”。羧基末端结构域沿中央离子孔排列，并且通道因细胞质中的收缩而关闭。弯曲的螺旋梁和锚域将压电重复序列与孔连接起来，并准备好进行变构控制门控。该结构为进一步剖析压电是如何被机械力调节提供了一个跳板。
Piezo1 and Piezo2 are mechanically activated ion channels that mediate touch perception, proprioception, and vascular development. Piezos are distinct from other ion channels and their structure remains poorly defined, impeding detailed study of their gating and ion permeation properties. Here, we report a high-resolution cryo-electron microscopy structure of the mouse Piezo1 trimer. The detergent-solubilized complex adopts a three-blade propeller shape with a curved transmembrane region containing at least 26 transmembrane helices per protomer. The flexible propeller blades can adopt distinct conformations, and consist of a series of four-transmembrane helix bundles we term ‘Piezo Repeats’. Carboxy-terminal domains line the central ion pore, and the channel is closed by constrictions in the cytosol. A kinked helical beam and anchor domain link the Piezo Repeats to the pore, and are poised to allosterically control gating. The structure provides a springboard to further dissect how Piezos are regulated by mechanical force.