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1edh

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Revision as of 11:47, 20 November 2007 by OCA (Talk | contribs)
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1edh, resolution 2.0Å

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E-CADHERIN DOMAINS 1 AND 2 IN COMPLEX WITH CALCIUM

Overview

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.

About this Structure

1EDH is a Single protein structure of sequence from Mus musculus with HG and CA as ligands. Full crystallographic information is available from OCA.

Reference

Structural basis of calcium-induced E-cadherin rigidification and dimerization., Nagar B, Overduin M, Ikura M, Rini JM, Nature. 1996 Mar 28;380(6572):360-4. PMID:8598933

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