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1edh

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(New page: 200px<br /><applet load="1edh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1edh, resolution 2.0&Aring;" /> '''E-CADHERIN DOMAINS 1 ...)
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[[Image:1edh.gif|left|200px]]<br /><applet load="1edh" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1edh, resolution 2.0&Aring;" />
caption="1edh, resolution 2.0&Aring;" />
'''E-CADHERIN DOMAINS 1 AND 2 IN COMPLEX WITH CALCIUM'''<br />
'''E-CADHERIN DOMAINS 1 AND 2 IN COMPLEX WITH CALCIUM'''<br />
==Overview==
==Overview==
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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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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==
==About this Structure==
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1EDH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with HG and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EDH OCA].
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1EDH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=HG:'>HG</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EDH OCA].
==Reference==
==Reference==
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[[Category: Nagar, B.]]
[[Category: Nagar, B.]]
[[Category: Overduin, M.]]
[[Category: Overduin, M.]]
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[[Category: Rini, J.M.]]
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[[Category: Rini, J M.]]
[[Category: CA]]
[[Category: CA]]
[[Category: HG]]
[[Category: HG]]
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[[Category: cell adhesion protein]]
[[Category: cell adhesion protein]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:55:07 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:26:41 2008''

Revision as of 10:26, 21 February 2008


1edh, resolution 2.0Å

Drag the structure with the mouse to rotate

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 and 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

Page seeded by OCA on Thu Feb 21 12:26:41 2008

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