|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5jym' size='340' side='right'caption='[[5jym]], [[Resolution|resolution]] 2.45Å' scene=''> | | <StructureSection load='5jym' size='340' side='right'caption='[[5jym]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jym]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JYM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JYM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jym]] 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=5JYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JYM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jyl|5jyl]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDH3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5jym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jym OCA], [https://pdbe.org/5jym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jym RCSB], [https://www.ebi.ac.uk/pdbsum/5jym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jym ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5jym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jym OCA], [http://pdbe.org/5jym PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jym RCSB], [http://www.ebi.ac.uk/pdbsum/5jym PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jym ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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. | + | [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 == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 26: |
| | *[[Cadherin 3D structures|Cadherin 3D structures]] | | *[[Cadherin 3D structures|Cadherin 3D structures]] |
| | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Caaveiro, J M.M]] | + | [[Category: Caaveiro JMM]] |
| - | [[Category: Kudo, S]] | + | [[Category: Kudo S]] |
| - | [[Category: Tsumoto, K]] | + | [[Category: Tsumoto K]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Cadherin]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Cell adhesion-immune system complex]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Protein-protein interaction]]
| + | |
| Structural highlights
Disease
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
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kudo S, Caaveiro JM, Nagatoishi S, Miyafusa T, Matsuura T, Sudou Y, Tsumoto K. Disruption of cell adhesion by an antibody targeting the cell-adhesive intermediate (X-dimer) of human P-cadherin. Sci Rep. 2017 Jan 3;7:39518. doi: 10.1038/srep39518. PMID:28045038 doi:http://dx.doi.org/10.1038/srep39518
|
