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-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 alpha- and beta-catenin in vitro and then visualized them by electron microscopy after rotary shadowing. Calculated solution 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. Co-precipitation and surface plasmon resonance assays localize the site of alpha-catenin dimerization to the NH2-terminal 228 amino acids. This region encompasses a high-affinity (Kd = 100 nM) binding site for beta-catenin that lies between residues 54 and 157. We anticipate that the oligomeric state of alpha-catenin and the relative stoichiometry of the components in the membrane adhesion complex will be dynamic and regulated by beta-catenin, cell adhesion, and probably other factors as well.
Koslov
E R
ER
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Maupin
P
P
Pradhan
D
D
Morrow
J S
JS
Rimm
D L
DL
D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism; D002846:Chromatography, Affinity; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D019281:Dimerization; D005982:Glutathione Transferase; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012044:Regression Analysis; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D005982:Glutathione Transferase