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| | <StructureSection load='4qd2' size='340' side='right'caption='[[4qd2]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='4qd2' size='340' side='right'caption='[[4qd2]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qd2]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Clobh Clobh] 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=4QD2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QD2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qd2]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum_A_str._Hall Clostridium botulinum A str. Hall] 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=4QD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QD2 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]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ha70, CBO0801, CLC_0857 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=441771 CLOBH]), ha17, CBO0802, CLC_0858 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=441771 CLOBH]), ha33, CBO0803, CLC_0859 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=441771 CLOBH]), Cdh1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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='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=4qd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd2 OCA], [http://pdbe.org/4qd2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qd2 RCSB], [http://www.ebi.ac.uk/pdbsum/4qd2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qd2 ProSAT]</span></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=4qd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd2 OCA], [https://pdbe.org/4qd2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qd2 RCSB], [https://www.ebi.ac.uk/pdbsum/4qd2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qd2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CADH1_MOUSE CADH1_MOUSE]] 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 (By similarity). E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production (By similarity). | + | [https://www.uniprot.org/uniprot/A5HZZ6_CLOBH A5HZZ6_CLOBH] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Cadherin 3D structures|Cadherin 3D structures]] | | *[[Cadherin 3D structures|Cadherin 3D structures]] |
| - | *[[Hemagglutinin|Hemagglutinin]] | + | *[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Clobh]] | + | [[Category: Clostridium botulinum A str. Hall]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Dong, M]] | + | [[Category: Dong M]] |
| - | [[Category: Dorner, M B]] | + | [[Category: Dorner MB]] |
| - | [[Category: Gu, S]] | + | [[Category: Gu S]] |
| - | [[Category: Jin, R]] | + | [[Category: Jin R]] |
| - | [[Category: Kruel, A]] | + | [[Category: Kruel A]] |
| - | [[Category: Lee, K]] | + | [[Category: Lee K]] |
| - | [[Category: Perry, K]] | + | [[Category: Perry K]] |
| - | [[Category: Rummel, A]] | + | [[Category: Rummel A]] |
| - | [[Category: Zhong, X]] | + | [[Category: Zhong X]] |
| - | [[Category: Botulinum neurotoxin]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: E-cadherin]]
| + | |
| - | [[Category: Ha17]]
| + | |
| - | [[Category: Ha33]]
| + | |
| - | [[Category: Ha70]]
| + | |
| - | [[Category: Oral toxicity]]
| + | |
| Structural highlights
Function
A5HZZ6_CLOBH
Publication Abstract from PubMed
How botulinum neurotoxins (BoNTs) cross the host intestinal epithelial barrier in foodborne botulism is poorly understood. Here, we present the crystal structure of a clostridial hemagglutinin (HA) complex of serotype BoNT/A bound to the cell adhesion protein E-cadherin at 2.4 angstroms. The HA complex recognizes E-cadherin with high specificity involving extensive intermolecular interactions and also binds to carbohydrates on the cell surface. Binding of the HA complex sequesters E-cadherin in the monomeric state, compromising the E-cadherin-mediated intercellular barrier and facilitating paracellular absorption of BoNT/A. We reconstituted the complete 14-subunit BoNT/A complex using recombinantly produced components and demonstrated that abolishing either E-cadherin- or carbohydrate-binding of the HA complex drastically reduces oral toxicity of BoNT/A complex in vivo. Together, these studies establish the molecular mechanism of how HAs contribute to the oral toxicity of BoNT/A.
Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex.,Lee K, Zhong X, Gu S, Kruel AM, Dorner MB, Perry K, Rummel A, Dong M, Jin R Science. 2014 Jun 20;344(6190):1405-10. doi: 10.1126/science.1253823. PMID:24948737[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lee K, Zhong X, Gu S, Kruel AM, Dorner MB, Perry K, Rummel A, Dong M, Jin R. Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex. Science. 2014 Jun 20;344(6190):1405-10. doi: 10.1126/science.1253823. PMID:24948737 doi:http://dx.doi.org/10.1126/science.1253823
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