α-catenin can form asymmetric homodimeric complexes and/or heterodimeric complexes with β-catenin

Abstract

The cadherin-based transmembrane cell-cell adhesive complex is thought to be composed of a cadherin molecule, a β-catenin, and an α-catenin, which connects the complex to the cytoskeleton. The precise stoichiometry of this complex remains uncertain. We have used a series of recombinant molecules and biophysical techniques to assess the multimeric state of human α- and β- catenin in vitro and then visualized them by electron microscopy after rotary shadowing. Calculated solution molecular masses are 213 kDa for α-catenin, 73 kDa for β-catenin, and 186 kDa for both. This suggests that α-catenin exists as a homodimer in solution, β-catenin is a monomer, and when both are present, they form α/β-catenin heterodimers. Co-precipitation and surface plasmon resonance assays localize the site of α-catenin dimerization to the NH2-terminal 228 amino acids. This region encompasses a high-affinity (K(d) = 100 nM) binding site for β-catenin that lies between residues 54 and 157. We anticipate that the oligomeric state of α-catenin and the relative stoichiometry of the components in the membrane adhesion complex will be dynamic and regulated by β-catenin, cell adhesion, and probably other factors as well.