Quantitative prediction and measurement of Piezo's membrane footprint.
Quantitative prediction and measurement of Piezo's membrane footprint.
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DOI：
10.1073/pnas.2208027119
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发表时间：
2022-10-04
影响因子：
11.1
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中科院分区：
文献类型：
--
作者：
过去五十年的研究已经产生了一个关于膜蛋白如何使脂质双层变形的美丽物理理论，类似于薄弹性壳的弯曲。由此产生的蛋白质膜足迹已被提出在蛋白质调节、膜重塑和膜组织中发挥重要的生物学作用。但是，通过直接比较预测和测量的膜足迹来测试和进一步发展双层-蛋白质相互作用的膜弹性理论一直具有挑战性。我们定量地测量了压电蛋白如何使脂双层囊泡变形，并表明这些囊泡的形状可以通过膜弹性理论准确地预测。我们提供了一个通用的方法，潜在的广泛适用性，研究蛋白质如何耦合到膜形状。压电蛋白是机械敏感的离子通道，可以局部地将膜弯曲成圆顶形状[Y。R.郭河，巴西-地MacKinnon，eLife 6，e33660（2017）]。压电圆顶的弯曲形状预期使周围的脂质双层膜变形成膜足迹，这可以用于放大压电对施加的力的灵敏度[C. A.哈塞尔万特河MacKinnon，eLife 7，e41968（2018）]。如果压电蛋白包埋在脂质双层囊泡中，由压电圆顶引起的膜形状变形取决于囊泡的大小。我们在这里采用膜弹性理论来预测，没有自由参数，这种压电囊泡的形状外的压电圆顶，并表明，预测的囊泡形状同意定量与相应的测量囊泡形状通过冷冻电子断层扫描获得，为一系列的囊泡尺寸[W. Helfrich，Z.自然的。C 28，693-703（1973）]。在此基础上，我们探讨了压电和膜形状之间的耦合，并证明了影响压电膜足迹的压电圆顶的功能近似遵循球冠几何形状。我们的工作奠定了从膜形状测量中推导压电圆顶关键弹性特性的基础，并为量化蛋白质如何使双层膜变形提供了一个通用框架。
Studies over the past five decades have yielded a beautiful physical theory of how membrane proteins deform lipid bilayers, akin to the bending of a thin elastic shell. The resulting membrane footprints of proteins have been proposed to play important biological roles in protein regulation, membrane remodeling, and membrane organization. But it has been challenging to test and further develop the membrane elasticity theory of bilayer–protein interactions through direct comparison of predicted and measured membrane footprints. We quantitatively measure how Piezo proteins deform lipid bilayer vesicles, and show that the shape of these vesicles can be predicted accurately through membrane elasticity theory. We provide a general approach, of potentially wide applicability, for studying how proteins couple to membrane shape. Piezo proteins are mechanosensitive ion channels that can locally curve the membrane into a dome shape [Y. R. Guo, R. MacKinnon, eLife 6, e33660 (2017)]. The curved shape of the Piezo dome is expected to deform the surrounding lipid bilayer membrane into a membrane footprint, which may serve to amplify Piezo’s sensitivity to applied forces [C. A. Haselwandter, R. MacKinnon, eLife 7, e41968 (2018)]. If Piezo proteins are embedded in lipid bilayer vesicles, the membrane shape deformations induced by the Piezo dome depend on the vesicle size. We employ here membrane elasticity theory to predict, with no free parameters, the shape of such Piezo vesicles outside the Piezo dome, and show that the predicted vesicle shapes agree quantitatively with the corresponding measured vesicle shapes obtained through cryoelectron tomography, for a range of vesicle sizes [W. Helfrich, Z. Naturforsch. C 28, 693–703 (1973)]. On this basis, we explore the coupling between Piezo and membrane shape and demonstrate that the features of the Piezo dome affecting Piezo’s membrane footprint approximately follow a spherical cap geometry. Our work puts into place the foundation for deducing key elastic properties of the Piezo dome from membrane shape measurements and provides a general framework for quantifying how proteins deform bilayer membranes.
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影响因子：
3
作者：
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通讯作者：
Fernandez, Jose-Jesus
影响因子：
7.7
作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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