An ensemble of flexible conformations underlies mechanotransduction by the cadherin-catenin adhesion complex
An ensemble of flexible conformations underlies mechanotransduction by the cadherin-catenin adhesion complex
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DOI：
10.1073/pnas.1911489116
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发表时间：
2019-10-22
影响因子：
11.1
通讯作者：
Bu, Zimei
中科院分区：
文献类型：
--
作者：
Bush, Martin;Alhanshali, Bashir M.;Bu, Zimei
钙粘蛋白-连环蛋白粘附复合物是细胞-细胞粘附连接的中心组分，其将机械应力从细胞传递到细胞。我们已经确定了由α-连环蛋白，β-连环蛋白，上皮钙粘蛋白胞质结构域（ABE）形成的粘附连接复合物的纳米级结构，使用负染电子显微镜，小角X射线散射，和选择性氘化/小角中子散射。ABE复合物是高度柔韧的，并显示出广泛的柔性结构，这是由α-和β-连环蛋白中的蛋白质结构域运动促进的。此外，β-连环蛋白的107个残基固有无序的N-末端区段形成柔性“舌”，其插入α-连环蛋白中并参与ABE复合物的组装。ABE复合物的柔性构象的未预料到的合奏表明，除了在机械张力下由ABE复合物显示的捕获/滑动键行为之外，在转换机械信号时的灵敏度和可逆性的动态机制。我们的研究结果提供了机械的洞察力的结构动力学的钙粘蛋白-连环蛋白粘附复合体在mechanotransduction。
The cadherin-catenin adhesion complex is the central component of the cell-cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the alpha-catenin.beta-catenin.epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in alpha- and beta-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of beta-catenin forms a flexible "tongue" that is inserted into alpha-catenin and participates in the assembly of the ABE complex. The unanticipated ensemble of flexible conformations of the ABE complex suggests a dynamic mechanism for sensitivity and reversibility when transducing mechanical signals, in addition to the catch/slip bond behavior displayed by the ABE complex under mechanical tension. Our results provide mechanistic insight into the structural dynamics for the cadherin-catenin adhesion complex in mechanotransduction.