Force-induced conformational changes in PIEZO1,Nature

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Force-induced conformational changes in PIEZO1
Nature ( IF 50.5 ) Pub Date : 2019-08-21 , DOI: 10.1038/s41586-019-1499-2
Yi-Chih Lin _{1,

2} , Yusong R Guo ₃ , Atsushi Miyagi _{1,

2} , Jesper Levring ₃ , Roderick MacKinnon ₃ , Simon Scheuring _{1,

2}

Affiliation

PIEZO1 is a mechanosensitive channel that converts applied force into electrical signals. Partial molecular structures show that PIEZO1 is a bowl-shaped trimer with extended arms. Here we use cryo-electron microscopy to show that PIEZO1 adopts different degrees of curvature in lipid vesicles of different sizes. We also use high-speed atomic force microscopy to analyse the deformability of PIEZO1 under force in membranes on a mica surface, and show that PIEZO1 can be flattened reversibly into the membrane plane. By approximating the absolute force applied, we estimate a range of values for the mechanical spring constant of PIEZO1. Both methods of microscopy demonstrate that PIEZO1 can deform its shape towards a planar structure. This deformation could explain how lateral membrane tension can be converted into a conformation-dependent change in free energy to gate the PIEZO1 channel in response to mechanical perturbations.Cryo-electron microscopy and high-speed atomic force microscopy reveal that PIEZO1 can reversibly deform its shape towards a planar structure, which may explain how the PIEZO1 channel is gated in response to mechanical stimulation.

中文翻译：

力诱导的 PIEZO1 构象变化

PIEZO1 是一种机械敏感通道，可将施加的力转换为电信号。部分分子结构显示PIEZO1是一个具有延伸臂的碗形三聚体。在这里，我们使用冷冻电子显微镜显示PIEZO1在不同大小的脂质囊泡中采用不同程度的曲率。我们还使用高速原子力显微镜分析了云母表面膜中 PIEZO1 在力作用下的变形能力，并表明 PIEZO1 可以可逆地压平到膜平面中。通过近似施加的绝对力，我们估计了 PIEZO1 机械弹簧常数的一系列值。两种显微镜方法都证明 PIEZO1 可以将其形状变形为平面结构。这种变形可以解释横向膜张力如何转化为构象依赖性自由能变化，以响应机械扰动来控制 PIEZO1 通道。冷冻电子显微镜和高速原子力显微镜揭示 PIEZO1 可以可逆地变形其形状朝向平面结构，这可以解释 PIEZO1 通道如何响应机械刺激而被门控。

更新日期：2019-08-21

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