6c0b
From Proteopedia
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<StructureSection load='6c0b' size='340' side='right' caption='[[6c0b]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='6c0b' size='340' side='right' caption='[[6c0b]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6c0b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C0B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C0B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6c0b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_difficilis"_hall_and_o'toole_1935 "bacillus difficilis" hall and o'toole 1935] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C0B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C0B FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tcdB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1496 "Bacillus difficilis" Hall and O'Toole 1935]), FZD2 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6c0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c0b OCA], [http://pdbe.org/6c0b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c0b RCSB], [http://www.ebi.ac.uk/pdbsum/6c0b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c0b 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=6c0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c0b OCA], [http://pdbe.org/6c0b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c0b RCSB], [http://www.ebi.ac.uk/pdbsum/6c0b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c0b ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/FZD2_HUMAN FZD2_HUMAN]] Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. | [[http://www.uniprot.org/uniprot/FZD2_HUMAN FZD2_HUMAN]] Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Clostridium difficile infection is the most common cause of antibiotic-associated diarrhea in developed countries. The major virulence factor, C. difficile toxin B (TcdB), targets colonic epithelia by binding to the frizzled (FZD) family of Wnt receptors, but how TcdB recognizes FZDs is unclear. Here, we present the crystal structure of a TcdB fragment in complex with the cysteine-rich domain of human FZD2 at 2.5-angstrom resolution, which reveals an endogenous FZD-bound fatty acid acting as a co-receptor for TcdB binding. This lipid occupies the binding site for Wnt-adducted palmitoleic acid in FZDs. TcdB binding locks the lipid in place, preventing Wnt from engaging FZDs and signaling. Our findings establish a central role of fatty acids in FZD-mediated TcdB pathogenesis and suggest strategies to modulate Wnt signaling. | ||
| + | |||
| + | Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B.,Chen P, Tao L, Wang T, Zhang J, He A, Lam KH, Liu Z, He X, Perry K, Dong M, Jin R Science. 2018 May 11;360(6389):664-669. doi: 10.1126/science.aar1999. PMID:29748286<ref>PMID:29748286</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6c0b" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bacillus difficilis hall and o'toole 1935]] | ||
| + | [[Category: Human]] | ||
[[Category: Chen, P]] | [[Category: Chen, P]] | ||
[[Category: Jin, R]] | [[Category: Jin, R]] | ||
Revision as of 07:44, 23 May 2018
Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B
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