ALPHA-CATENIN CAN FORM ASYMMETRIC HOMODIMERIC COMPLEXES AND OR HETERODIMERIC COMPLEXES WITH BETA-CATENIN/

The cadherin-based transmembrane cell-cell adhesive complex is thought to be composed of a cadherin molecule, a beta-catenin, and an alpha-c atenin, which connects the complex to the cytoskeleton. The precise st oichiometry of this complex remains uncertain. We have used a series o f recombinant molecules and biophysical techniques to assess the multi meric state of human alpha- and beta-catenin in vitro and then visuali zed them by electron microscopy after rotary shadowing. Calculated sol ution molecular masses are 213 kDa for alpha-catenin, 73 kDa for beta- catenin, and 186 kDa for both, This suggests that alpha-catenin exists as a homodimer in solution, beta-catenin is a monomer, and when both are present, they form alpha/beta-catenin heterodimers. Go-precipitati on and surface plasmon resonance assays localize the site of alpha-cat enin dimerization to the NH2-terminal 228 amino acids. This region enc ompasses a high-affinity (K-d = 100 nM) binding site for beta-catenin that lies between residues 54 and 157. We anticipate that the oligomer ic state of alpha-catenin and the relative stoichiometry of the compon ents in the membrane adhesion complex will be dynamic and regulated by beta-catenin, cell adhesion, and probably other factors as well.