The three-dimensional structure of the cadherin-catenin complex

Subcell Biochem. 2012:60:39-62. doi: 10.1007/978-94-007-4186-7_3.

Abstract

The cadherin-catenin complex is the major building block of the adherens junction. It is responsible for coupling Ca(2+)-dependent intercellular junctions with various intracellular events, including actin dynamics and signaling pathways. Determination of three-dimensional structures of cadherins, p120 catenin, β-catenin and α-catenin at atomic-level resolution has allowed us to examine how the structure and function of cell adhesion molecules are further modulated by protein-protein interactions. Structural studies of cadherins revealed the strand-swap-dependent and -independent trans-dimerization mechanisms, as well as a potential mechanism for lateral clustering of cadherin trans-dimers. Crystallographic and NMR analyses of p120 catenin revealed that it regulates the stability of cadherin-mediated cell-cell adhesion by associating with the majority of the E-cadherin juxtamembrane domain, including residues implicated in clathrin-mediated endocytosis and Hakai-dependent ubiquitination. Crystal structures of the β-catenin/E-cadherin complex and the β-/α-catenin chimera revealed extensive interactions necessary to form the cadherin/β-catenin/α-catenin ternary complex. Structural characterization of α-catenin has revealed conformational changes within the N-terminal and modulatory domains that are crucial for its role as a mechanosensor of cell-cell adhesion. Further insights into the connection between the cadherin-catenin complex and the actin cytoskeleton are integral to better understand how adjoining cells communicate through cell-cell adhesion.

Publication types

  • Review

MeSH terms

  • Animals
  • Cadherins / chemistry*
  • Cadherins / metabolism
  • Catenins / chemistry*
  • Catenins / metabolism
  • Cell Adhesion / physiology*
  • Humans
  • Protein Conformation

Substances

  • Cadherins
  • Catenins