View source for 7stz


==Crystal Structure of Human E-cadherin EC1-5 bound by mouse monoclonal antibody Fab mAb-1_19A11==
<StructureSection load='7stz' size='340' side='right'caption='[[7stz]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7stz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7STZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7STZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7stz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7stz OCA], [https://pdbe.org/7stz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7stz RCSB], [https://www.ebi.ac.uk/pdbsum/7stz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7stz ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CADH1_HUMAN CADH1_HUMAN] Defects in CDH1 are the cause of hereditary diffuse gastric cancer (HDGC) [MIM:[https://omim.org/entry/137215 137215]. An autosomal dominant cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Note=Heterozygous germline mutations CDH1 are responsible for familial cases of diffuse gastric cancer. Somatic mutations in the has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer.<ref>PMID:10319582</ref> <ref>PMID:12216071</ref>   Defects in CDH1 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[https://omim.org/entry/608089 608089].  Defects in CDH1 are a cause of susceptibility to ovarian cancer (OC) [MIM:[https://omim.org/entry/167000 167000]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
== Function ==
[https://www.uniprot.org/uniprot/CADH1_HUMAN CADH1_HUMAN] Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.<ref>PMID:16417575</ref>   E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production.<ref>PMID:16417575</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
E-cadherin adhesion is regulated at the cell surface, a process that can be replicated by activating antibodies. We use cryo-electron microscopy (EM) and X-ray crystallography to examine functional states of the cadherin adhesive dimer. This dimer is mediated by N-terminal beta strand-swapping involving Trp2, and forms via a different transient X-dimer intermediate. X-dimers are observed in cryo-EM along with monomers and strand-swap dimers, indicating that X-dimers form stable interactions. A novel EC4-mediated dimer was also observed. Activating Fab binding caused no gross structural changes in E-cadherin monomers, but can facilitate strand swapping. Moreover, activating Fab binding is incompatible with the formation of the X-dimer. Both cryo-EM and X-ray crystallography reveal a distinctive twisted strand-swap dimer conformation caused by an outward shift in the N-terminal beta strand that may represent a strengthened state. Thus, regulation of adhesion involves changes in cadherin dimer configurations.

Regulation of multiple dimeric states of E-cadherin by adhesion activating antibodies revealed through Cryo-EM and X-ray crystallography.,Maker A, Bolejack M, Schecterson L, Hammerson B, Abendroth J, Edwards TE, Staker B, Myler PJ, Gumbiner BM PNAS Nexus. 2022 Aug 19;1(4):pgac163. doi: 10.1093/pnasnexus/pgac163. eCollection , 2022 Sep. PMID:36157596<ref>PMID:36157596</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7stz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cadherin 3D structures|Cadherin 3D structures]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Structural genomic]]