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| | ==Crystal structure of human claudin-4 in complex with C-terminal fragment of Clostridium perfringens enterotoxin== | | ==Crystal structure of human claudin-4 in complex with C-terminal fragment of Clostridium perfringens enterotoxin== |
| - | <StructureSection load='5b2g' size='340' side='right' caption='[[5b2g]], [[Resolution|resolution]] 3.50Å' scene=''> | + | <StructureSection load='5b2g' size='340' side='right'caption='[[5b2g]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5b2g]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B2G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B2G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5b2g]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens], [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B2G FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 3.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3x29|3x29]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=5b2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b2g OCA], [http://pdbe.org/5b2g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b2g RCSB], [http://www.ebi.ac.uk/pdbsum/5b2g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b2g 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=5b2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b2g OCA], [https://pdbe.org/5b2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b2g RCSB], [https://www.ebi.ac.uk/pdbsum/5b2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b2g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/CLD4_HUMAN CLD4_HUMAN] CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4]] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.<ref>PMID:22389108</ref> [[http://www.uniprot.org/uniprot/ELTB_CLOPF ELTB_CLOPF]] This enterotoxin is responsible for many cases of a mild type of food poisoning. | + | [https://www.uniprot.org/uniprot/CLD4_HUMAN CLD4_HUMAN] Channel-forming tight junction protein that mediates paracellular chloride transport in the kidney. Plays a critical role in the paracellular reabsorption of filtered chloride in the kidney collecting ducts. Claudins play a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.[UniProtKB:O35054][https://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.<ref>PMID:22389108</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Kimura-Someya, T]] | + | [[Category: Clostridium perfringens]] |
| - | [[Category: Shinoda, T]] | + | [[Category: Escherichia virus T4]] |
| - | [[Category: Shirouzu, M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Yokoyama, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Cell-free protein expression system]] | + | [[Category: Kimura-Someya T]] |
| - | [[Category: Complex]] | + | [[Category: Shinoda T]] |
| - | [[Category: Membrane protein]] | + | [[Category: Shirouzu M]] |
| | + | [[Category: Yokoyama S]] |
| Structural highlights
Disease
CLD4_HUMAN CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.
Function
CLD4_HUMAN Channel-forming tight junction protein that mediates paracellular chloride transport in the kidney. Plays a critical role in the paracellular reabsorption of filtered chloride in the kidney collecting ducts. Claudins play a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.[UniProtKB:O35054]ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[1]
Publication Abstract from PubMed
The food-poisoning bacterium Clostridium perfringens produces an enterotoxin (~35 kDa) that specifically targets human claudin-4, among the 26 human claudin proteins, and causes diarrhea by fluid accumulation in the intestinal cavity. The C-terminal domain of the Clostridium perfringens enterotoxin (C-CPE, ~15 kDa) binds tightly to claudin-4, and disrupts the intestinal tight junction barriers. In this study, we determined the 3.5-A resolution crystal structure of the cell-free synthesized human claudin-4*C-CPE complex, which is significantly different from the structure of the off-target complex of an engineered C-CPE with mouse claudin-19. The claudin-4*C-CPE complex structure demonstrated the mechanism underlying claudin assembly disruption. A comparison of the present C-CPE-bound structure of claudin-4 with the enterotoxin-free claudin-15 structure revealed sophisticated C-CPE-induced conformation changes of the extracellular segments, induced on the foundation of the rigid four-transmembrane-helix bundle structure. These conformation changes provide a mechanistic model for the disruption of the lateral assembly of claudin molecules. Furthermore, the present novel structural mechanism for selecting a specific member of the claudin family can be used as the foundation to develop novel medically important technologies to selectively regulate the tight junctions formed by claudin family members in different organs.
Structural basis for disruption of claudin assembly in tight junctions by an enterotoxin.,Shinoda T, Shinya N, Ito K, Ohsawa N, Terada T, Hirata K, Kawano Y, Yamamoto M, Kimura-Someya T, Yokoyama S, Shirouzu M Sci Rep. 2016 Sep 20;6:33632. doi: 10.1038/srep33632. PMID:27647526[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. Protein determinants of phage T4 lysis inhibition. Protein Sci. 2012 Apr;21(4):571-82. doi: 10.1002/pro.2042. Epub 2012 Mar 2. PMID:22389108 doi:http://dx.doi.org/10.1002/pro.2042
- ↑ Shinoda T, Shinya N, Ito K, Ohsawa N, Terada T, Hirata K, Kawano Y, Yamamoto M, Kimura-Someya T, Yokoyama S, Shirouzu M. Structural basis for disruption of claudin assembly in tight junctions by an enterotoxin. Sci Rep. 2016 Sep 20;6:33632. doi: 10.1038/srep33632. PMID:27647526 doi:http://dx.doi.org/10.1038/srep33632
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