4nc2
From Proteopedia
(Difference between revisions)
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==Crystal structure of TcdB-B1 bound to B39 VHH== | ==Crystal structure of TcdB-B1 bound to B39 VHH== | ||
- | <StructureSection load='4nc2' size='340' side='right' caption='[[4nc2]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4nc2' size='340' side='right'caption='[[4nc2]], [[Resolution|resolution]] 2.50Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>[[4nc2]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[4nc2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NC2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NC2 FirstGlance]. <br> |
- | </td></tr> | + | </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=4nc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nc2 OCA], [https://pdbe.org/4nc2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nc2 RCSB], [https://www.ebi.ac.uk/pdbsum/4nc2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nc2 ProSAT]</span></td></tr> |
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- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == Function == | ||
- | [ | + | [https://www.uniprot.org/uniprot/TCDB_CLODI TCDB_CLODI] Precursor of a cytotoxin that targets and disrupts the colonic epithelium, inducing the host inflammatory and innate immune responses and resulting in diarrhea and pseudomembranous colitis (PubMed:20844489, PubMed:24919149). TcdB constitutes the main toxin that mediates the pathology of C.difficile infection, an opportunistic pathogen that colonizes the colon when the normal gut microbiome is disrupted (PubMed:19252482, PubMed:20844489). Compared to TcdA, TcdB is more virulent and more important for inducing the host inflammatory and innate immune responses (PubMed:19252482, PubMed:24919149). This form constitutes the precursor of the toxin: it enters into host cells and mediates autoprocessing to release the active toxin (Glucosyltransferase TcdB) into the host cytosol (PubMed:10768933, PubMed:11152463, PubMed:12941936, PubMed:17334356, PubMed:20498856). Targets colonic epithelia by binding to the frizzled receptors FZD1, FZD2 and FZD7, and enters host cells via clathrin-mediated endocytosis (PubMed:27680706). Frizzled receptors constitute the major host receptors in the colonic epithelium, but other receptors, such as CSPG4 or NECTIN3/PVRL3, have been identified (PubMed:25547119, PubMed:26038560, PubMed:27680706). Binding to carbohydrates and sulfated glycosaminoglycans on host cell surface also contribute to entry into cells (By similarity). Once entered into host cells, acidification in the endosome promotes the membrane insertion of the translocation region and formation of a pore, leading to translocation of the GT44 and peptidase C80 domains across the endosomal membrane (PubMed:11152463, PubMed:12941936, PubMed:24567384). This activates the peptidase C80 domain and autocatalytic processing, releasing the N-terminal part (Glucosyltransferase TcdB), which constitutes the active part of the toxin, in the cytosol (PubMed:17334356, PubMed:27571750).[UniProtKB:P16154]<ref>PMID:10768933</ref> <ref>PMID:11152463</ref> <ref>PMID:12941936</ref> <ref>PMID:17334356</ref> <ref>PMID:19252482</ref> <ref>PMID:20498856</ref> <ref>PMID:20844489</ref> <ref>PMID:24567384</ref> <ref>PMID:24919149</ref> <ref>PMID:25547119</ref> <ref>PMID:26038560</ref> <ref>PMID:27571750</ref> <ref>PMID:27680706</ref> Active form of the toxin, which is released into the host cytosol following autoprocessing and inactivates small GTPases (PubMed:8144660, PubMed:7777059, PubMed:16157585, PubMed:17901056, PubMed:24905543, PubMed:24919149). Acts by mediating monoglucosylation of small GTPases of the Rho family (Rac1, RhoA, RhoB, RhoC, RhoG and Cdc42) in host cells at the conserved threonine residue located in the switch I region ('Thr-37/35'), using UDP-alpha-D-glucose as the sugar donor (PubMed:7777059, PubMed:16157585, PubMed:17901056, PubMed:24905543, PubMed:24919149). Monoglucosylation of host small GTPases completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death, resulting in the loss of colonic epithelial barrier function (PubMed:7777059, PubMed:24919149).<ref>PMID:16157585</ref> <ref>PMID:17901056</ref> <ref>PMID:24905543</ref> <ref>PMID:24919149</ref> <ref>PMID:7777059</ref> <ref>PMID:8144660</ref> |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 4nc2" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4nc2" style="background-color:#fffaf0;"></div> | ||
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+ | ==See Also== | ||
+ | *[[Antibody 3D structures|Antibody 3D structures]] | ||
+ | *[[3D structures of non-human antibody|3D structures of non-human antibody]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
- | [[Category: | + | [[Category: Clostridioides difficile]] |
- | [[Category: | + | [[Category: Lama glama]] |
- | [[Category: Eugenio | + | [[Category: Large Structures]] |
- | [[Category: Hussack | + | [[Category: Eugenio L]] |
- | [[Category: Kitova | + | [[Category: Hussack G]] |
- | [[Category: Klassen | + | [[Category: Kitova EN]] |
- | [[Category: Murase | + | [[Category: Klassen JS]] |
- | [[Category: Ng | + | [[Category: Murase T]] |
- | [[Category: Schorr | + | [[Category: Ng KKS]] |
- | [[Category: Tanha | + | [[Category: Schorr M]] |
- | + | [[Category: Tanha J]] | |
- | + |
Revision as of 08:20, 11 January 2023
Crystal structure of TcdB-B1 bound to B39 VHH
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Categories: Clostridioides difficile | Lama glama | Large Structures | Eugenio L | Hussack G | Kitova EN | Klassen JS | Murase T | Ng KKS | Schorr M | Tanha J