Identification of a binding site for integrin alpha E beta(7) in the N-terminal domain of E-cadherin

The integrin alpha E beta 7, which is predominantly expressed on mucosal T lymphocytes, has recently been shown to recognize the cell adhesion molecule, E-cadherin, on epithelial cells. We have carried out mutations on E-cadherin, involving domain deletions as web as substitutions of specific amino acids, in order to identify the sites recognized by the integrin. Binding of alpha E beta 7 required the presence of the first two N-terminal domains of E-cadherin, Deletion of extracellular domains 3 and 4 or truncation of the cytoplasmic domain of E-cadherin had no consequence on integrin binding, Substitution of a glutamic acid in the BC loop of the Ig structure of the fist, N-terminal, domain of E-cadherin abrogated binding of alpha E beta 7. This mutation did not appear to affect the conformation of the domain nor the pattern of expression of E-cadherin on the cell surface, Synthetic peptides encompassing the first domain of E-cadherin had very little inhibitory effect on the interaction with alpha E beta 7. Our results highlight structural dissimilarities between recognition of E-cadherin by alpha E beta 7 and recognition of other members of the IgSF by integrins and show that the heterophilic (integrin binding) and homophilic sites in the N-terminal domain of E-cadherin are distinct.