钙粘蛋白
化学
二聚体
细胞粘附
生物物理学
单克隆抗体
粘附
细胞粘附分子
细胞生物学
细胞
抗体
生物化学
生物
免疫学
有机化学
作者
Bin Xie,Sai Xu,Leslayann Schecterson,Barry M. Gumbiner,Sanjeevi Sivasankar
标识
DOI:10.1016/j.str.2023.11.002
摘要
E-cadherins (Ecads) are a crucial cell-cell adhesion protein with tumor suppression properties. Ecad adhesion can be enhanced by the monoclonal antibody 66E8, which has potential applications in inhibiting cancer metastasis. However, the biophysical mechanisms underlying 66E8-mediated adhesion strengthening are unknown. Here, we use molecular dynamics simulations, site-directed mutagenesis, and single-molecule atomic force microscopy experiments to demonstrate that 66E8 strengthens Ecad binding by stabilizing the primary Ecad adhesive conformation: the strand-swap dimer. By forming electrostatic interactions with Ecad, 66E8 stabilizes the swapped β-strand and its hydrophobic pocket and impedes Ecad conformational changes, which are necessary for rupture of the strand-swap dimer. Our findings identify fundamental mechanistic principles for strengthening of Ecad binding using monoclonal antibodies.
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