Structure deformation and curvature sensing of PIEZO1 in lipid membranes
Structure deformation and curvature sensing of PIEZO1 in lipid membranes
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DOI：
10.1038/s41586-022-04574-8
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发表时间：
2022-04-06
期刊：
影响因子：
64.8
通讯作者：
Xiao, Bailong
中科院分区：
文献类型：
--
作者：
Yang, Xuzhong;Lin, Chao;Xiao, Bailong
PIEZO通道响应于微微牛顿尺度的力来介导关键的生理和病理生理过程（1-5）。洗涤剂溶解的PIEZO通道形成碗状三聚体，其包含具有细胞外帽的中心离子传导孔和具有细胞内梁的三个弯曲且非平面的叶片（6-10），其可以在脂质膜内经历力诱导的变形（11）。然而，脂质膜中PIEZO通道门控动力学的结构和机制仍然没有得到解决。在这里，我们确定了PIEZO 1在脂质体囊泡中重构的弯曲和扁平结构，直接可视化了PIEZO 1-脂质双层系统的显著变形性和扁平结构中约300 nm（2）的面内面积膨胀。PIEZO 1的弯曲结构类似于洗涤剂胶束确定的结构，但具有许多结合的磷脂。相比之下，扁平结构表现出膜张力诱导的叶片扁平化、梁弯曲以及帽的分离和旋转，这可能共同导致离子传导路径的门控。根据测量的PIEZO 1的平面内膜面积膨胀和刚度常数（参考文献10），(11))我们计算出半最大活化张力约为1.9 pN nm（-1），与实验测量值相匹配。因此，我们的研究提供了对PIEZO 1的显著变形性和结构重排如何在脂质膜中实现精致的机械敏感性和独特的基于曲率的门控的基本理解。
PIEZO channels respond to piconewton-scale forcesto mediate critical physiological and pathophysiological processes(1-5). Detergent-solubilized PIEZO channels form bowl-shaped trimers comprising a central ion-conducting pore with an extracellular cap and three curved and non-planar blades with intracellular beams(6-10), which may undergo force-induced deformation within lipid membranes(11). However, the structures and mechanisms underlying the gating dynamics of PIEZO channels in lipid membranes remain unresolved. Here we determine the curved and flattened structures of PIEZO1 reconstituted in liposome vesicles, directly visualizing the substantial deformability of the PIEZO1-lipid bilayer system and an in-plane areal expansion of approximately 300 nm(2) in the flattened structure. The curved structure of PIEZO1 resembles the structure determined from detergent micelles, but has numerous bound phospholipids. By contrast, the flattened structure exhibits membrane tension-induced flattening of the blade, bending of the beam and detaching and rotating of he cap, which could collectively lead to gating of the ion-conducting pathway. On the basis of the measured in-plane membrane area expansion and stiffness constant of PIEZO1 (ref.(11)), we calculate a half maximal activation tension of about 1.9 pN nm(-1) , matching experimentally measured values. Thus, our studies provide a fundamental understanding of how the notable deformability and structural rearrangement of PIEZO1 achieve exquisite mechanosensitivity and unique curvature-based gating in lipid membranes.