Elastic properties and shape of the Piezo dome underlying its mechanosensory function.
Elastic properties and shape of the Piezo dome underlying its mechanosensory function.
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DOI：
10.1073/pnas.2208034119
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发表时间：
2022-10-04
影响因子：
11.1
通讯作者：
MacKinnon, Roderick
中科院分区：
文献类型：
--
作者：
Haselwandtera, Christoph A.;Guoc, Yusong R.;Fuc, Ziao;MacKinnon, Roderick
在过去的二十年里，结构生物学为膜蛋白的形状提供了很多见解。然而，除了形状之外，膜蛋白的功能还取决于蛋白质的弹性。它一直很难在独立的，未扰动的脂质双层膜，这是最相关的细胞膜的情况下，蛋白质的弹性特性的特征。在这里，我们表明，通过物理上的理解蛋白质如何变形的脂质双层膜，它是可以推断出弹性的膜蛋白质的膜形状的观察。在此基础上，我们提供了机械敏感离子通道Piezo的张力依赖性激活的生物物理原理和机制，该离子通道介导触觉和许多其他重要的生物过程。我们在配套文件中表明，含有机械敏感离子通道压电的脂质双层囊泡的自由膜形状可以通过膜弹性理论以及蛋白质几何形状和囊泡大小的测量来预测，而不需要自由参数[C. A. Haselwandter，Y. R. Guo，Z.富河，巴西-地MacKinnon，Proc. Natl. Acad. Sci.美国，10.1073/pnas.2208027119（2022）]。在这里，我们使用这些结果来确定的力，压电圆顶施加在自由膜，因此，自由膜施加在压电圆顶，为一系列的囊泡大小。从囊泡形状测量单独，我们因此获得的压电圆顶，从中我们推导出的压电圆顶的固有曲率半径，nm，和弯曲刚度，在独立的脂质双层膜模仿细胞膜的力-变形关系。将这些估计应用于嵌入脂质双层中的压电的球冠模型，我们建议压电的固有曲率，周围的膜足迹，小刚度和大面积的压电的关键属性，引起低阈值，高灵敏度的机械门控。
Over the past two decades, structural biology has provided much insight into the shape of membrane proteins. Beyond shape, however, membrane protein function can also depend on the protein’s elastic properties. It has been difficult to characterize protein elastic properties in freestanding, unperturbed lipid bilayer membranes, which is the scenario most relevant for cell membranes. Here we show that, through a physical understanding of how proteins deform lipid bilayer membranes, it is possible to deduce elastic properties of membrane proteins solely from observations of membrane shape. On this basis, we provide the biophysical principles and mechanisms underlying the tension-dependent activation of the mechanosensitive ion channel Piezo, which mediates the sensation of touch and many other important biological processes. We show in the companion paper that the free membrane shape of lipid bilayer vesicles containing the mechanosensitive ion channel Piezo can be predicted, with no free parameters, from membrane elasticity theory together with measurements of the protein geometry and vesicle size [C. A. Haselwandter, Y. R. Guo, Z. Fu, R. MacKinnon, Proc. Natl. Acad. Sci. U.S.A., 10.1073/pnas.2208027119 (2022)]. Here we use these results to determine the force that the Piezo dome exerts on the free membrane and hence, that the free membrane exerts on the Piezo dome, for a range of vesicle sizes. From vesicle shape measurements alone, we thus obtain a force–distortion relationship for the Piezo dome, from which we deduce the Piezo dome’s intrinsic radius of curvature, nm, and bending stiffness, , in freestanding lipid bilayer membranes mimicking cell membranes. Applying these estimates to a spherical cap model of Piezo embedded in a lipid bilayer, we suggest that Piezo’s intrinsic curvature, surrounding membrane footprint, small stiffness, and large area are the key properties of Piezo that give rise to low-threshold, high-sensitivity mechanical gating.
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影响因子：
64.8
作者：
Yang, Xuzhong;Lin, Chao;Xiao, Bailong
通讯作者：
Xiao, Bailong
DOI：
10.1111/nyas.12874
发表时间：
2015-01-01
期刊：
ANNALS REPORTS, VOL 1352
影响因子：
--
作者：
Brohawn, Stephen G.
通讯作者：
Brohawn, Stephen G.
影响因子：
7.7
作者：
Guo YR;MacKinnon R
通讯作者：
MacKinnon R
DOI：
10.1073/pnas.1320768111
发表时间：
2014-03-04
影响因子：
11.1
作者：
Brohawn, Stephen G.;Su, Zhenwei;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
64.8
作者：
Saotome K;Murthy SE;Kefauver JM;Whitwam T;Patapoutian A;Ward AB
通讯作者：
Ward AB