Structural basis for homophilic adhesion by cadherins and by myelin p0

In many instances the organization of cells into tissues involves interactions between like molecules from the contacting cell surfaces. Homophilic adhesion can also be important between membrane surfaces of the same cell as in the myelin sheath covering nerve axons. The molecules that subserve these extracellular interactions traverse the membrane, and cytoplasmic portions may mediate other interactions, which in the case of cadherins are to cytoskeletal elements such as actin filaments. We have determined the structure of an adhesive domain of N-cadherin in three crystal lattices, all of which exhibit a common interdigitated ribbon of these domains. The features of this ribbon are like those expected for the natural cell-cell interface, which we describe as a cell adhesion zipper. We have also determined the crystal structure of the P0 adhesion domain from peripheral nerve myelin. Here as well, features of the packing appear to relate to the natural adhesive interaction. Cooperative superstructures such as these may in general provide a mechanism to marshal individually weak molecular interactions into strong bonds between cells.