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Publication Abstract from PubMed

The classical cadherin-beta-catenin-alpha-catenin complex mediates homophilic cell-cell adhesion and mechanically couples the actin cytoskeletons of adjacent cells. Although alpha-catenin binds to beta-catenin and to F-actin, beta-catenin significantly weakens the affinity of alpha-catenin for F-actin. Moreover, alpha-catenin self-associates into homodimers that block beta-catenin binding. We investigated quantitatively and structurally alphaE- and alphaN-catenin dimer formation, their interaction with beta-catenin and the cadherin-beta-catenin complex, and the effect of the alpha-catenin actin-binding domain on beta-catenin association. The two alpha-catenin variants differ in their self-association properties: at physiological temperatures alphaE-catenin homodimerizes 10x more weakly than does alphaN-catenin, but is kinetically trapped in its oligomeric state. Both alphaE- and alphaN-catenin bind to beta-catenin with a Kd of 20 nM, and this affinity is increased by an order of magnitude when cadherin is bound to beta-catenin. We describe the crystal structure of a complex representing the full beta-catenin-alphaN-catenin interface. A three-dimensional model of the cadherin-beta-catenin-alpha-catenin complex based on these new structural data suggests mechanisms for the enhanced stability of the ternary complex. The C-terminal actin-binding domain of alpha-catenin has no influence on the interactions with beta-catenin, arguing against models in which beta-catenin weakens actin binding by stabilizing inhibitory intramolecular interactions between the actin-binding domain and the rest of alpha-catenin.

Structural and Thermodynamic Characterization of Cadherin-beta-catenin-alpha-catenin Complex Formation.,Pokutta S, Choi HJ, Ahlsen G, Hansen SD, Weis WI J Biol Chem. 2014 Apr 1. PMID:24692547^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.