View source for 5jyl


==Human P-cadherin MEC1 with scFv TSP7 bound==
<StructureSection load='5jyl' size='340' side='right'caption='[[5jyl]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jyl]] is a 4 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=5JYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JYL 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]] 2.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5jyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jyl OCA], [https://pdbe.org/5jyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jyl RCSB], [https://www.ebi.ac.uk/pdbsum/5jyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jyl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CADH3_HUMAN CADH3_HUMAN] Hypotrichosis with juvenile macular degeneration;EEM syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/CADH3_HUMAN CADH3_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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human P-cadherin is a cell adhesion protein of the family of classical cadherins, the overexpression of which is correlated with poor prognosis in various types of cancer. Antibodies inhibiting cell-cell adhesion mediated by P-cadherin show clear therapeutic effect, although the mechanistic basis explaining their effectiveness is still unclear. Based on structural, physicochemical, and functional analyses, we have elucidated the molecular mechanism of disruption of cell adhesion by antibodies targeting human P-cadherin. Herein we have studied three different antibodies, TSP5, TSP7, and TSP11, each recognizing a different epitope on the surface of the cell-adhesive domain (EC1). Although all these three antibodies recognized human P-cadherin with high affinity, only TSP7 disrupted cell adhesion. Notably, we demonstrated that TSP7 abolishes cell adhesion by disabling the so-called X-dimer (a kinetic adhesive intermediate), in addition to disrupting the strand-swap dimer (the final thermodynamic state). The inhibition of the X-dimer was crucial for the overall inhibitory effect, raising the therapeutic value of a kinetic intermediary not only for preventing, but also for reversing, cell adhesion mediated by a member of the classical cadherin family. These findings should help to design more innovative and effective therapeutic solutions targeting human P-cadherin.

Disruption of cell adhesion by an antibody targeting the cell-adhesive intermediate (X-dimer) of human P-cadherin.,Kudo S, Caaveiro JM, Nagatoishi S, Miyafusa T, Matsuura T, Sudou Y, Tsumoto K Sci Rep. 2017 Jan 3;7:39518. doi: 10.1038/srep39518. PMID:28045038<ref>PMID:28045038</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5jyl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Cadherin 3D structures|Cadherin 3D structures]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Caaveiro JMM]]
[[Category: Kudo S]]
[[Category: Tsumoto K]]