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| | <StructureSection load='6a7h' size='340' side='right'caption='[[6a7h]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='6a7h' size='340' side='right'caption='[[6a7h]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6a7h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Vibvu Vibvu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A7H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6A7H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6a7h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_vulnificus_CMCP6 Vibrio vulnificus CMCP6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A7H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A7H FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.301Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6a7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a7h OCA], [http://pdbe.org/6a7h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a7h RCSB], [http://www.ebi.ac.uk/pdbsum/6a7h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a7h ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6a7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a7h OCA], [https://pdbe.org/6a7h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a7h RCSB], [https://www.ebi.ac.uk/pdbsum/6a7h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a7h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A0A452CSN9_VIBVU A0A452CSN9_VIBVU] |
| - | Multifunctional autoprocessing repeats-in-toxin (MARTX) toxins are secreted by Gram-negative bacteria and function as primary virulence-promoting macromolecules that deliver multiple cytopathic and cytotoxic effector domains into the host cytoplasm. Among these effectors, Ras/Rap1-specific endopeptidase (RRSP) catalyzes the sequence-specific cleavage of the switch I region of the cellular substrates Ras and Rap1 that are crucial for host innate immune defenses during infection. To dissect the molecular basis underpinning RRSP-mediated substrate inactivation, we determined the crystal structure of an RRSP from the sepsis-causing bacterial pathogen Vibrio vulnificus (VvRRSP). Structural and biochemical analyses revealed that VvRRSP is a metal-independent TIKI family endopeptidase composed of an N-terminal membrane-localization and substrate-recruitment domain (N lobe) connected via an inter-lobe linker to the C-terminal active site-coordinating core beta-sheet-containing domain (C lobe). Structure-based mutagenesis identified the 2His/2Glu catalytic residues in the core catalytic domain that are shared with other TIKI family enzymes and that are essential for Ras processing. In vitro KRas cleavage assays disclosed that deleting the N lobe in VvRRSP causes complete loss of enzymatic activity. Endogenous Ras cleavage assays combined with confocal microscopy analysis of HEK293T cells indicated that the N lobe functions both in membrane localization via the first alpha helix and in substrate assimilation by altering the functional conformation of the C lobe to facilitate recruitment of cellular substrates. Collectively, these results indicate that RRSP is a critical virulence factor that robustly inactivates Ras and Rap1 and augments the pathogenicity of invading bacteria via the combined effects of its N and C lobes.
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| - | | + | |
| - | Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1-specific endopeptidase from the sepsis-causing pathogen Vibrio vulnificus.,Jang SY, Hwang J, Kim BS, Lee EY, Oh BH, Kim MH J Biol Chem. 2018 Oct 3. pii: RA118.004857. doi: 10.1074/jbc.RA118.004857. PMID:30282804<ref>PMID:30282804</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6a7h" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Vibvu]] | + | [[Category: Vibrio vulnificus CMCP6]] |
| - | [[Category: Hwang, J]] | + | [[Category: Hwang J]] |
| - | [[Category: Jang, S Y]] | + | [[Category: Jang SY]] |
| - | [[Category: Kim, M H]] | + | [[Category: Kim MH]] |
| - | [[Category: Protein toxin]]
| + | |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Virulence]]
| + | |
