2vkd
From Proteopedia
(Difference between revisions)
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<StructureSection load='2vkd' size='340' side='right'caption='[[2vkd]], [[Resolution|resolution]] 2.53Å' scene=''> | <StructureSection load='2vkd' size='340' side='right'caption='[[2vkd]], [[Resolution|resolution]] 2.53Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2vkd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[2vkd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Paeniclostridium_sordellii Paeniclostridium sordellii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VKD FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.53Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</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=2vkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vkd OCA], [https://pdbe.org/2vkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vkd RCSB], [https://www.ebi.ac.uk/pdbsum/2vkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vkd 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=2vkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vkd OCA], [https://pdbe.org/2vkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vkd RCSB], [https://www.ebi.ac.uk/pdbsum/2vkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vkd ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TCSL1_PAESO TCSL1_PAESO] Precursor of a cytotoxin that targets the vascular endothelium, inducing an anti-inflammatory effect and resulting in lethal toxic shock syndrome (PubMed:19527792, PubMed:24919149, PubMed:29146177). TcsL constitutes the main toxin that mediates the pathology of P.sordellii infection, an anaerobic Gram-positive bacterium found in soil and in the gastrointestinal and vaginal tracts of animals and humans; although the majority of carriers are asymptomatic, pathogenic P.sordellii infections arise rapidly and are highly lethal (PubMed:29146177). This form constitutes the precursor of the toxin: it enters into host cells and mediates autoprocessing to release the active toxin (Glucosyltransferase TcsL) into the host cytosol (PubMed:32302524, PubMed:17334356, PubMed:27303685). Targets vascular endothelium by binding to the semaphorin proteins SEMA6A and SEMA6B, and enters host cells via clathrin-mediated endocytosis (PubMed:32302524). 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 (By similarity). This activates the peptidase C80 domain and autocatalytic processing, releasing the N-terminal part (Glucosyltransferase TcsL), which constitutes the active part of the toxin, in the cytosol (PubMed:17334356, PubMed:27303685).[UniProtKB:P18177]<ref>PMID:17334356</ref> <ref>PMID:19527792</ref> <ref>PMID:24919149</ref> <ref>PMID:27303685</ref> <ref>PMID:32302524</ref> <ref>PMID:29146177</ref> Active form of the toxin, which is released into the host cytosol following autoprocessing and inactivates small GTPases (PubMed:8626575, PubMed:8626586, PubMed:9632667, PubMed:17901056, PubMed:19744486, PubMed:24905543, PubMed:24919149, PubMed:27303685, PubMed:27023605, PubMed:30622517). Acts by mediating monoglucosylation of small GTPases of the Ras (H-Ras/HRAS, K-Ras/KRAS, N-Ras/NRAS and Ral/RALA) family 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:8858106, PubMed:8626575, PubMed:8626586, PubMed:9632667, PubMed:17901056, PubMed:19744486, PubMed:24905543, PubMed:24919149, PubMed:27023605, PubMed:30622517). Also able to catalyze monoglucosylation of some members of the Rho family (Rac1 and Rap2A), but with less efficiency than with Ras proteins (PubMed:8626586, PubMed:9632667, PubMed:19744486, PubMed:24905543). Monoglucosylation of host small GTPases completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form and leading to apoptosis (PubMed:8626586, PubMed:9632667, PubMed:17910886). Induces an anti-inflammatory effect, mainly by inactivating Ras proteins which results in blockage of the cell cycle and killing of immune cells (PubMed:17910886, PubMed:24919149). The absence or moderate local inflammatory response allows C.sordellii spreading in deep tissues, production of toxin which is released in the general circulation and causes a toxic shock syndrome (PubMed:24919149, PubMed:29146177).<ref>PMID:17901056</ref> <ref>PMID:17910886</ref> <ref>PMID:19744486</ref> <ref>PMID:24905543</ref> <ref>PMID:24919149</ref> <ref>PMID:27023605</ref> <ref>PMID:27303685</ref> <ref>PMID:30622517</ref> <ref>PMID:8626575</ref> <ref>PMID:8626586</ref> <ref>PMID:8858106</ref> <ref>PMID:9632667</ref> <ref>PMID:29146177</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Bacillus oedematis sporogenes sordelli 1923]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Paeniclostridium sordellii]] |
| - | [[Category: | + | [[Category: Aktories K]] |
| - | [[Category: | + | [[Category: Jank T]] |
| - | [[Category: | + | [[Category: Schulz GE]] |
| - | [[Category: | + | [[Category: Ziegler MOP]] |
| - | + | ||
Current revision
CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF LETHAL TOXIN FROM CLOSTRIDIUM SORDELLII IN COMPLEX WITH UDP-GLC AND MANGANESE ION
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