Structure-based membrane dome mechanism for Piezo mechanosensitivity.
Structure-based membrane dome mechanism for Piezo mechanosensitivity.
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DOI：
10.7554/elife.33660
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发表时间：
2017-12-12
期刊：
影响因子：
7.7
通讯作者：
MacKinnon R
中科院分区：
文献类型：
--
作者：
Guo YR;MacKinnon R
机械敏感离子通道将外部机械刺激转化为电化学信号，用于关键过程，包括触觉，平衡和心血管调节。最好理解的机械敏感通道，MscL，打开一个宽的孔，这是由于平面内面积扩张造成的机械敏感门控。真核压电通道具有狭窄的孔，因此必须捕获机械力以另一种方式控制门控。我们提出了一个冷冻电镜结构的小鼠Piezo 1在一个封闭的构象，在3.7纳米分辨率。该通道是一个三重离子，其臂由围绕孔的4-TM结构单元的重复阵列组成。它的形状使膜局部变形成圆顶。我们提出了一个假设，其中的膜变形的变化后，通道开放。定量地说，膜张力将改变门控能量学，与圆顶下投影面积的变化成比例。这种机制可以解释高度敏感的机械门控在一个狭窄的，阳离子选择性孔的设置。
Mechanosensitive ion channels convert external mechanical stimuli into electrochemical signals for critical processes including touch sensation, balance, and cardiovascular regulation. The best understood mechanosensitive channel, MscL, opens a wide pore, which accounts for mechanosensitive gating due to in-plane area expansion. Eukaryotic Piezo channels have a narrow pore and therefore must capture mechanical forces to control gating in another way. We present a cryo-EM structure of mouse Piezo1 in a closed conformation at 3.7Å-resolution. The channel is a triskelion with arms consisting of repeated arrays of 4-TM structural units surrounding a pore. Its shape deforms the membrane locally into a dome. We present a hypothesis in which the membrane deformation changes upon channel opening. Quantitatively, membrane tension will alter gating energetics in proportion to the change in projected area under the dome. This mechanism can account for highly sensitive mechanical gating in the setting of a narrow, cation-selective pore.