LAUSR

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 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.