Laboratory of Molecular Electron Microscopy, The Rockefeller University, New York, NY 10065.
Department of Chemistry and Biochemistry, City College of New York, City University of New York, New York, NY 10031.
Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21545-21555. doi: 10.1073/pnas.1911489116. Epub 2019 Oct 7.
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 α-catenin•β-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 α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible "tongue" that is inserted into α-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.
钙黏蛋白-catenin 黏附复合体是细胞-细胞黏附连接点的核心组成部分，可将机械应力从一个细胞传递到另一个细胞。我们使用负染色电子显微镜、小角度 X 射线散射和选择性氘化/小角中子散射技术，确定了由α-catenin•β-catenin•上皮钙黏蛋白胞质域（ABE）形成的黏着连接复合体的纳米级结构。ABE 复合体具有高度柔韧性，并显示出广泛的灵活结构，这得益于 α-和 β-catenin 中的蛋白结构域运动。此外，β-catenin 的 107 个残基无规则的 N 端片段形成一个灵活的“舌”，插入到 α-catenin 中，并参与 ABE 复合体的组装。ABE 复合体出乎意料的灵活构象集合表明，在机械信号转导过程中，除了 ABE 复合体在机械张力下表现出的“捕捉/滑动”键行为外，还存在一种敏感和可逆的动态机制。我们的研究结果为机械转导过程中钙黏蛋白-catenin 黏附复合体的结构动力学提供了机制见解。
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