4ONS

Structural and thermodynamic characterization of cadherin-beta-catenin-alpha-catenin complex formation

Summary for 4ONS

• Entry DOI: 10.2210/pdb4ons/pdb
• Descriptor: Catenin alpha-2, Catenin beta-1 (3 entities in total)
• Functional Keywords: four helix bundles, cell adhesion
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm (By similarity): Q61301; Cytoplasm: Q02248
• Total number of polymer chains: 4
• Total formula weight: 74528.68

Authors

Pokutta, S.,Choi, H.-J.,Ahlsen, G.,Hansen, S.D.,Weis, W.I. (deposition date: 2014-01-29, release date: 2014-04-09, Last modification date: 2024-02-28)

Primary citation

Pokutta, S.,Choi, H.J.,Ahlsen, G.,Hansen, S.D.,Weis, W.I.
Structural and Thermodynamic Characterization of Cadherin beta-Catenin alpha-Catenin Complex Formation.
J.Biol.Chem., 289:13589-13601, 2014

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

PubMed: 24692547
DOI: 10.1074/jbc.M114.554709

Experimental method

X-RAY DIFFRACTION (2.8 Å)