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PDBsum entry 1edh
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Cell adhesion protein
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PDB id
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1edh
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis of calcium-Induced e-Cadherin rigidification and dimerization.
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Authors
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B.Nagar,
M.Overduin,
M.Ikura,
J.M.Rini.
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Ref.
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Nature, 1996,
380,
360-364.
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PubMed id
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Abstract
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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.
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