2o72
From Proteopedia
(New page: 200px<br /> <applet load="2o72" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o72, resolution 2.000Å" /> '''Crystal Structure ...) |
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caption="2o72, resolution 2.000Å" /> | caption="2o72, resolution 2.000Å" /> | ||
'''Crystal Structure Analysis of human E-cadherin (1-213)'''<br /> | '''Crystal Structure Analysis of human E-cadherin (1-213)'''<br /> | ||
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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== | ||
| - | 2O72 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2O72 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O72 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: metal binding protein]] | [[Category: metal binding protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:00:15 2008'' |
Revision as of 11:00, 23 January 2008
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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 with as ligand. 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
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