STRUCTURE-FUNCTION ANALYSIS OF CELL-ADHESION BY NEURAL (N-) CADHERIN

To investigate the possible biological function of the lateral ''stran d dimer'' observed in crystal structures of a D1 domain extracellular fragment from N-cadherin, we have undertaken site-directed mutagenesis studies of this molecule. Mutation of most residues important in the strand dimer interface abolish the ability of N-cadherin to mediate ce ll adhesion. Mutation of an analogous central residue (Trp-2) in E-cad herin also abrogates the adhesive capacity of that molecule. We also d etermined the crystal structure of a Ca2+-complexed two-domain fragmen t from N-cadherin. This structure, like its E-cadherin counterpart, do es not adopt the strand dimer conformation. This suggests the possibil ity that classical cadherins might stably exist in both dimeric and mo nomeric forms. Data from several laboratories imply that:lateral dimer ization or clustering of cadherins may increase their adhesivity. We s uggest the possibility that the strand dimer may play a role in this a ctivation.