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| | ==VirA-Rab1 complex structure== | | ==VirA-Rab1 complex structure== |
| - | <StructureSection load='4fmb' size='340' side='right' caption='[[4fmb]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='4fmb' size='340' side='right'caption='[[4fmb]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fmb]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Shigella_flexneri Shigella flexneri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FMB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FMB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fmb]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Shigella_flexneri Shigella flexneri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FMB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FMB FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fma|4fma]], [[4fmc|4fmc]], [[4fmd|4fmd]], [[4fme|4fme]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CP0181, pWR501_0191, virA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=623 Shigella flexneri]), RAB1, RAB1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4fmb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fmb OCA], [https://pdbe.org/4fmb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fmb RCSB], [https://www.ebi.ac.uk/pdbsum/4fmb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fmb ProSAT]</span></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fmb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fmb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fmb RCSB], [http://www.ebi.ac.uk/pdbsum/4fmb PDBsum]</span></td></tr>
| + | </table> |
| - | <table> | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/VIRA_SHIFL VIRA_SHIFL] Alpha-tubulin-specific protease that is required for entry into epithelial cells and for subsequent intra- and intercellular spreading. Contributes to bacterial entry into epithelial cells by inducing microtubule (MT) destabilization and the formation of membrane ruffles. The membrane ruffling evoked by VirA results from the activation of host rac1, which is associated with the destruction of MT networks. Creates a tunnel inside the host cell cytoplasm by breaking down the microtubule infrastructure. This facilitates the bacterium's movement through the cytoplasm and also helps other bacteria move faster during the invasion of the eukaryotic cell. Is absolutely required for virulence.<ref>PMID:7494473</ref> <ref>PMID:12065406</ref> <ref>PMID:17095701</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4fmb" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Shigella flexneri]] | | [[Category: Shigella flexneri]] |
| - | [[Category: Shao, F.]] | + | [[Category: Shao F]] |
| - | [[Category: Zhu, Y.]] | + | [[Category: Zhu Y]] |
| - | [[Category: Alpha-beta fold]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Rab1]]
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| - | [[Category: Rab1-gap complex]]
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| Structural highlights
Function
VIRA_SHIFL Alpha-tubulin-specific protease that is required for entry into epithelial cells and for subsequent intra- and intercellular spreading. Contributes to bacterial entry into epithelial cells by inducing microtubule (MT) destabilization and the formation of membrane ruffles. The membrane ruffling evoked by VirA results from the activation of host rac1, which is associated with the destruction of MT networks. Creates a tunnel inside the host cell cytoplasm by breaking down the microtubule infrastructure. This facilitates the bacterium's movement through the cytoplasm and also helps other bacteria move faster during the invasion of the eukaryotic cell. Is absolutely required for virulence.[1] [2] [3]
Publication Abstract from PubMed
Rab GTPases are frequent targets of vacuole-living bacterial pathogens for appropriate trafficking of the vacuole. Here we discover that bacterial effectors including VirA from nonvacuole Shigella flexneri and EspG from extracellular Enteropathogenic Escherichia coli (EPEC) harbor TBC-like dual-finger motifs and exhibits potent RabGAP activities. Specific inactivation of Rab1 by VirA/EspG disrupts ER-to-Golgi trafficking. S. flexneri intracellular persistence requires VirA TBC-like GAP activity that mediates bacterial escape from autophagy-mediated host defense. Rab1 inactivation by EspG severely blocks host secretory pathway, resulting in inhibited interleukin-8 secretion from infected cells. Crystal structures of VirA/EspG-Rab1-GDP-aluminum fluoride complexes highlight TBC-like catalytic role for the arginine and glutamine finger residues and reveal a 3D architecture distinct from that of the TBC domain. Structure of Arf6-EspG-Rab1 ternary complex illustrates a pathogenic signaling complex that rewires host Arf signaling to Rab1 inactivation. Structural distinctions of VirA/EspG further predict a possible extensive presence of TBC-like RabGAP effectors in counteracting various host defenses.
Structurally Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to Counteract Host Defenses.,Dong N, Zhu Y, Lu Q, Hu L, Zheng Y, Shao F Cell. 2012 Aug 31;150(5):1029-41. PMID:22939626[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Uchiya K, Tobe T, Komatsu K, Suzuki T, Watarai M, Fukuda I, Yoshikawa M, Sasakawa C. Identification of a novel virulence gene, virA, on the large plasmid of Shigella, involved in invasion and intercellular spreading. Mol Microbiol. 1995 Jul;17(2):241-50. PMID:7494473
- ↑ Yoshida S, Katayama E, Kuwae A, Mimuro H, Suzuki T, Sasakawa C. Shigella deliver an effector protein to trigger host microtubule destabilization, which promotes Rac1 activity and efficient bacterial internalization. EMBO J. 2002 Jun 17;21(12):2923-35. PMID:12065406 doi:10.1093/emboj/cdf319
- ↑ Yoshida S, Handa Y, Suzuki T, Ogawa M, Suzuki M, Tamai A, Abe A, Katayama E, Sasakawa C. Microtubule-severing activity of Shigella is pivotal for intercellular spreading. Science. 2006 Nov 10;314(5801):985-9. PMID:17095701 doi:10.1126/science.1133174
- ↑ Dong N, Zhu Y, Lu Q, Hu L, Zheng Y, Shao F. Structurally Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to Counteract Host Defenses. Cell. 2012 Aug 31;150(5):1029-41. PMID:22939626 doi:http://dx.doi.org/10.1016/j.cell.2012.06.050
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