1EDH

E-CADHERIN DOMAINS 1 AND 2 IN COMPLEX WITH CALCIUM

Summary for 1EDH

• Entry DOI: 10.2210/pdb1edh/pdb
• Descriptor: E-CADHERIN, MERCURY (II) ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: cadherin, cell adhesion protein, calcium binding protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Cell junction: P09803
• Total number of polymer chains: 2
• Total formula weight: 50078.66

Authors

Nagar, B.,Overduin, M.,Ikura, M.,Rini, J.M. (deposition date: 1996-05-15, release date: 1997-01-11, Last modification date: 2024-02-07)

Primary citation

Nagar, B.,Overduin, M.,Ikura, M.,Rini, J.M.
Structural basis of calcium-induced E-cadherin rigidification and dimerization.
Nature, 380:360-364, 1996

PubMed Abstract: 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.

PubMed: 8598933
DOI: 10.1038/380360a0

Experimental method

X-RAY DIFFRACTION (2 Å)