A SPECIFIC DOMAIN IN ALPHA-CATENIN MEDIATES BINDING TO BETA-CATENIN OR PLAKOGLOBIN

The E-cadherin-catenin adhesion complex has been the subject of many s tructural and functional studies because of its importance in developm ent, normal tissue function and carcinogenesis, It is well established that the cytoplasmic domain of E-cadherin binds either beta-catenin o r plakoglobin, which both can assemble alpha-catenin into the complex, Recently we have identified an alpha-catenin binding site in beta-cat enin and plakoglobin and postulated, based on sequence analysis, that these protein-protein interactions are mediated by a hydrophobic inter action mechanism, Here we have now identified the reciprocal complemen tary binding site in alpha-catenin which mediates its interaction with beta-catenin and plakoglobin, Using in vitro association assays with C-terminal truncations of alpha-catenin expressed as recombinant fusio n proteins, we found that the N-terminal 146 amino acids are required for this interaction, We then identified a peptide of 27 amino acids w ithin this sequence (amino acid positions 117-143) which is necessary and sufficient to bind beta-catenin or plakoglobin. As shown by mutati onal analysis, hydrophobic amino acids within this binding site are im portant for the interaction, The results described here, together with our previous work, give strong support for the idea that these protei ns associate by hydrophobic interactions of two alpha-helices.