Structure of Cadherins

Cadherins are a superfamily of calcium-dependent cell adhesion molecules or CAMs .

All cadherins have a basic structure comprising a small C-terminal cytosolic domain, a single transmembrane domain, and multiple extracellular cadherin or EC domains.

These EC domains are linked to each other by flexible hinge regions, each with three calcium-binding pockets.

When calcium ions bind, the cadherin becomes rigid, enabling cis- and trans-binding to other cadherins.

In cis-binding, cadherins on the same cell can bind to each other forming clusters, while the interaction of the EC domains of cadherins on adjacent cells results in trans-binding.

The N-terminal EC domain, furthest from the membrane, called EC1, has a knob and pocket structure. During trans-binding, the knob of one EC1 fits into the pocket of another EC1 on the adjacent cell.

This makes cadherins of one type preferentially bind cadherins of the same type, a homophilic binding.

Although the interaction between a single pair of cadherins is relatively weak, the cadherin clusters can form a collectively strong trans-binding. Such complexes form anchoring cell junctions.