Cadherins can dimerize via asymmetric interactions.

Cadherins are essential cell-cell adhesion proteins that interact in two distinct conformations: X-dimers and strand-swap dimers. Both X-dimers and strand-swap dimers are thought to exclusively rely on symmetric sets of interactions between key amino acids on both cadherin binding partners. Here, we use single-molecule Atomic Force Microscopy (AFM) and computer simulations to show that symmetry in cadherin binding is dispensable and that cadherins can also interact in a novel conformation that asymmetrically incorporates key elements of both strand-swap dimers and X-dimers. Our results clarify the biophysical rules for cadherin binding and demonstrate that cadherins interact in a more diverse range of conformations than previously understood.

钙黏蛋白是重要的细胞 - 细胞黏附蛋白，它们以两种不同的构象相互作用：X - 二聚体和链交换二聚体。人们认为X - 二聚体和链交换二聚体都完全依赖于钙黏蛋白两个结合伙伴上关键氨基酸之间的对称相互作用组。在此，我们利用单分子原子力显微镜（AFM）和计算机模拟表明，钙黏蛋白结合中的对称性并非必需，并且钙黏蛋白还能以一种新的构象相互作用，该构象不对称地包含了链交换二聚体和X - 二聚体的关键要素。我们的结果阐明了钙黏蛋白结合的生物物理规则，并证明钙黏蛋白相互作用的构象范围比之前所了解的更为多样。