OCA at 08:19, 20 March 2024

2024-03-20T08:19:55Z

←Older revision		Revision as of 08:19, 20 March 2024
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-	'''Unreleased structure'''

-	~~The entry~~ 8qen is ~~ON HOLD until Paper Publication~~	+	==cryo-EM structure of apo Clostridioides difficile toxin B==
-		+	<StructureSection load='8qen' size='340' side='right'caption='[[8qen]], [[Resolution\|resolution]] 3.40Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[8qen]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QEN FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.4Å</td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=8qen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qen OCA], [https://pdbe.org/8qen PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qen RCSB], [https://www.ebi.ac.uk/pdbsum/8qen PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qen ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Clostridioides difficile]]
		+	[[Category: Large Structures]]
		+	[[Category: Bous J]]
		+	[[Category: Kinsolving J]]

OCA at 12:08, 20 September 2023

2023-09-20T12:08:02Z

←Older revision		Revision as of 12:08, 20 September 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8qen is ON HOLD	+	The entry 8qen is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8qen" [edit=sysop:move=sysop]

2023-09-06T04:37:32Z

Protected "8qen" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:37, 6 September 2023

OCA: New page: '''Unreleased structure''' The entry 8qen is ON HOLD Authors: Description: Category: Unreleased Structures

2023-09-06T04:37:29Z

New page: '''Unreleased structure''' The entry 8qen is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8qen is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8qen - Revision history

OCA at 08:19, 20 March 2024

OCA at 12:08, 20 September 2023

OCA: Protected "8qen" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8qen is ON HOLD Authors: Description: Category: Unreleased Structures