2o72
From Proteopedia
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|PDB= 2o72 |SIZE=350|CAPTION= <scene name='initialview01'>2o72</scene>, resolution 2.000Å | |PDB= 2o72 |SIZE=350|CAPTION= <scene name='initialview01'>2o72</scene>, resolution 2.000Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= CDH1, CDHE, UVO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CDH1, CDHE, UVO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o72 OCA], [http://www.ebi.ac.uk/pdbsum/2o72 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2o72 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Cell adhesion mediated by type I cadherins involves homophilic "trans" interactions that are thought to be brought about by a strand exchange mechanism involving the N-terminal extracellular domain. Here, we present the high-resolution crystal structure of the N-terminal two domains of human E-cadherin. Comparison of this structure with other type I cadherin structures reveals features that are likely to be critical to facilitate dimerization by strand exchange as well as dimer flexibility. We integrate this structural knowledge to provide a model for type I cadherin adhesive interactions. Intra-molecular docking of the conserved N-terminal "adhesion arm" into the acceptor pocket in monomeric E-cadherin appears largely identical to inter-molecular docking of the adhesion arm in adhesive trans dimers. A strained conformation of the adhesion arm in the monomer, however, may create an equilibrium between "open" and "closed" forms that primes the cadherin for formation of adhesive interactions, which are then stabilized by additional dimer-specific contacts. By contrast, in type II cadherins, strain in the adhesion arm appears absent and a much larger surface area is involved in trans adhesion, which may compensate the activation energy required to peel off the intra-molecularly docked arm. It seems that evolution has selected slightly different adhesion mechanisms for type I and type II cadherins. | Cell adhesion mediated by type I cadherins involves homophilic "trans" interactions that are thought to be brought about by a strand exchange mechanism involving the N-terminal extracellular domain. Here, we present the high-resolution crystal structure of the N-terminal two domains of human E-cadherin. Comparison of this structure with other type I cadherin structures reveals features that are likely to be critical to facilitate dimerization by strand exchange as well as dimer flexibility. We integrate this structural knowledge to provide a model for type I cadherin adhesive interactions. Intra-molecular docking of the conserved N-terminal "adhesion arm" into the acceptor pocket in monomeric E-cadherin appears largely identical to inter-molecular docking of the adhesion arm in adhesive trans dimers. A strained conformation of the adhesion arm in the monomer, however, may create an equilibrium between "open" and "closed" forms that primes the cadherin for formation of adhesive interactions, which are then stabilized by additional dimer-specific contacts. By contrast, in type II cadherins, strain in the adhesion arm appears absent and a much larger surface area is involved in trans adhesion, which may compensate the activation energy required to peel off the intra-molecularly docked arm. It seems that evolution has selected slightly different adhesion mechanisms for type I and type II cadherins. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Breast cancer, lobular OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Cleft lip with or without cleft palate, with gastric cancer, familial diffuse OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Endometrial carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Gastric cancer, familial diffuse OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Listeria monocytogenes, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]], Ovarian carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192090 192090]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Parisini, E.]] | [[Category: Parisini, E.]] | ||
[[Category: Wang, J H.]] | [[Category: Wang, J H.]] | ||
| - | [[Category: CA]] | ||
[[Category: calcium-binding protein]] | [[Category: calcium-binding protein]] | ||
[[Category: cell adhesion]] | [[Category: cell adhesion]] | ||
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[[Category: metal binding protein]] | [[Category: metal binding protein]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:13:37 2008'' |
Revision as of 01:13, 31 March 2008
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| , resolution 2.000Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | CDH1, CDHE, UVO (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure Analysis of human E-cadherin (1-213)
Overview
Cell adhesion mediated by type I cadherins involves homophilic "trans" interactions that are thought to be brought about by a strand exchange mechanism involving the N-terminal extracellular domain. Here, we present the high-resolution crystal structure of the N-terminal two domains of human E-cadherin. Comparison of this structure with other type I cadherin structures reveals features that are likely to be critical to facilitate dimerization by strand exchange as well as dimer flexibility. We integrate this structural knowledge to provide a model for type I cadherin adhesive interactions. Intra-molecular docking of the conserved N-terminal "adhesion arm" into the acceptor pocket in monomeric E-cadherin appears largely identical to inter-molecular docking of the adhesion arm in adhesive trans dimers. A strained conformation of the adhesion arm in the monomer, however, may create an equilibrium between "open" and "closed" forms that primes the cadherin for formation of adhesive interactions, which are then stabilized by additional dimer-specific contacts. By contrast, in type II cadherins, strain in the adhesion arm appears absent and a much larger surface area is involved in trans adhesion, which may compensate the activation energy required to peel off the intra-molecularly docked arm. It seems that evolution has selected slightly different adhesion mechanisms for type I and type II cadherins.
About this Structure
2O72 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of human E-cadherin domains 1 and 2, and comparison with other cadherins in the context of adhesion mechanism., Parisini E, Higgins JM, Liu JH, Brenner MB, Wang JH, J Mol Biol. 2007 Oct 19;373(2):401-11. Epub 2007 Aug 21. PMID:17850815
Page seeded by OCA on Mon Mar 31 04:13:37 2008
