Structural basis of calcium-induced E-cadherin rigidification and dimerization

Nature. 1996 Mar 28;380(6572):360-4. doi: 10.1038/380360a0.


The cadherins mediate cell adhesion and play a fundamental role in normal development. They participate in the maintenance of proper cell-cell contacts: for example, reduced levels of epithelial cadherin (E-cadherin) correlate with increased invasiveness in many human tumour cell types. The cadherins typically consist of five tandemly repeated extracellular domains, a single membrane-spanning segment and a cytoplasmic region. The N-terminal extracellular domains mediate cell-cell contact while the cytoplasmic region interacts with the cytoskeleton through the catenins. Cadherins depend on calcium for their function: removal of calcium abolishes adhesive activity, renders cadherins vulnerable to proteases (reviewed in ref. 4) and, in E-cadherin, induces a dramatic reversible conformational change in the entire extracellular region. We report here the X-ray crystal structure at 2.0 A resolution of the two N-terminal extracellular domains of E-cadherin in the presence of calcium. The structure reveals a two-fold symmetric dimer, each molecule of which binds a contiguous array of three bridged calcium ions. Not only do the bound calcium ions linearize and rigidify the molecule, they promote dimerization. Although the N-terminal domain of each molecule in the dimer is aligned in a parallel orientation, the interactions between them differ significantly from those found in the neural cadherin (N-cadherin) N-terminal domain (NCD1) structure. The E-cadherin dual-domain structure reported here defines the role played by calcium in the cadherin-mediated formation and maintenance of solid tissues.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biopolymers
  • Cadherins / chemistry*
  • Calcium / chemistry*
  • Crystallography, X-Ray
  • Escherichia coli
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Structure-Activity Relationship


  • Biopolymers
  • Cadherins
  • Recombinant Proteins
  • Calcium

Associated data