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| | ==Crystal structure of ExoT (residues 28 -77)- SpcS complex from Pseudomonas aeruginosa at 2.1 angstrom== | | ==Crystal structure of ExoT (residues 28 -77)- SpcS complex from Pseudomonas aeruginosa at 2.1 angstrom== |
| - | <StructureSection load='4jmf' size='340' side='right' caption='[[4jmf]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='4jmf' size='340' side='right'caption='[[4jmf]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jmf]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JMF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JMF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jmf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JMF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.099Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">exoT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE]), SpcS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jmf OCA], [http://pdbe.org/4jmf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jmf RCSB], [http://www.ebi.ac.uk/pdbsum/4jmf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jmf 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=4jmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jmf OCA], [https://pdbe.org/4jmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jmf RCSB], [https://www.ebi.ac.uk/pdbsum/4jmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jmf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/EXOT_PSEAE EXOT_PSEAE] Bifunctional effector protein that is secreted and delivered by the type III secretion system into eukaryotic target cells. The N-terminus encodes a GTPase-activating protein activity, whereas the C-terminus encodes an ADP-ribosyltransferase activity (PubMed:11298647). ADP-ribosylates several eukaryotic proteins including CT10 regulator of kinase (Crk) proteins (PubMed:12807879). In turn, induces atypical anoikis apoptosis by transforming Crk adaptor protein into a cytotoxin (PubMed:26020630). Affects host cell morphology by disrupting the actin cytoskeleton (PubMed:14688136). In addition to this activity, acts via its N-terminal region as a GTPase-activating protein (GAP) for host Rho GTPases including RhoA, Rac1, Cdc42 and Ras (PubMed:11895987). The GAP domain activity induces mitochondrial disruption in the target host cell by activating host caspases 3 and 9 that execute cellular death (PubMed:26451042). This activity also causes stress fiber disassembly (PubMed:11895987).<ref>PMID:11298647</ref> <ref>PMID:11895987</ref> <ref>PMID:12807879</ref> <ref>PMID:14688136</ref> <ref>PMID:26020630</ref> <ref>PMID:26451042</ref> |
| - | ExoT belongs to the family of type 3 secretion system (T3SS) effector toxins in Pseudomonas aeruginosa, known to be one of the major virulence determinant toxins that cause chronic and acute infections in immuno-compromised individuals, burn victims and cystic fibrosis patients. Here, we report the X-ray crystal structure of the amino terminal fragment of effector toxin ExoT, in complex with full-length homodimeric chaperone SpcS at 2.1 A resolution. The full-length dimeric chaperone SpcS has the conserved alpha-beta-beta-beta-alpha-beta-beta-alpha fold of class I chaperones, the characteristic hydrophobic patches for binding effector proteins and a conserved polar cavity at the dimeric interface. The stable crystallized amino terminal fragment of ExoT consists of a chaperone binding domain and a membrane localization domain that wraps around the dimeric chaperone. Site-directed mutagenesis experiments and a molecular dynamics study complement each other in revealing Asn65, Phe67 and Trp88 as critical dimeric interfacial residues that can strongly influence the effector-chaperone interactions. DATABASE: The atomic coordinates and structure factors of ExoT-SpcS complex (code 4JMF) have been deposited in the Protein Data Bank Japan (PDBj), Institute for Protein Research, Osaka University.
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| - | Interfacial residues of SpcS chaperone affects binding of effector toxin ExoT in Pseudomonas aeruginosa: novel insights from structural and computational studies.,Dey S, Datta S FEBS J. 2014 Jan 4. doi: 10.1111/febs.12704. PMID:24387107<ref>PMID:24387107</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div> | + | |
| - | <div class="pdbe-citations 4jmf" style="background-color:#fffaf0;"></div> | + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Exoenzyme|Exoenzyme]] | + | *[[Exoenzyme 3D structures|Exoenzyme 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pseae]] | + | [[Category: Large Structures]] |
| - | [[Category: Datta, S]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Dey, S]] | + | [[Category: Datta S]] |
| - | [[Category: T3ss]] | + | [[Category: Dey S]] |
| - | [[Category: Toxin-chaperone complex]]
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| - | [[Category: Type iii secretion system]]
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| - | [[Category: Virulent effector]]
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| Structural highlights
Function
EXOT_PSEAE Bifunctional effector protein that is secreted and delivered by the type III secretion system into eukaryotic target cells. The N-terminus encodes a GTPase-activating protein activity, whereas the C-terminus encodes an ADP-ribosyltransferase activity (PubMed:11298647). ADP-ribosylates several eukaryotic proteins including CT10 regulator of kinase (Crk) proteins (PubMed:12807879). In turn, induces atypical anoikis apoptosis by transforming Crk adaptor protein into a cytotoxin (PubMed:26020630). Affects host cell morphology by disrupting the actin cytoskeleton (PubMed:14688136). In addition to this activity, acts via its N-terminal region as a GTPase-activating protein (GAP) for host Rho GTPases including RhoA, Rac1, Cdc42 and Ras (PubMed:11895987). The GAP domain activity induces mitochondrial disruption in the target host cell by activating host caspases 3 and 9 that execute cellular death (PubMed:26451042). This activity also causes stress fiber disassembly (PubMed:11895987).[1] [2] [3] [4] [5] [6]
See Also
References
- ↑ Sundin C, Henriksson ML, Hallberg B, Forsberg A, Frithz-Lindsten E. Exoenzyme T of Pseudomonas aeruginosa elicits cytotoxicity without interfering with Ras signal transduction. Cell Microbiol. 2001 Apr;3(4):237-46. doi: 10.1046/j.1462-5822.2001.00108.x. PMID:11298647 doi:http://dx.doi.org/10.1046/j.1462-5822.2001.00108.x
- ↑ Kazmierczak BI, Engel JN. Pseudomonas aeruginosa ExoT acts in vivo as a GTPase-activating protein for RhoA, Rac1, and Cdc42. Infect Immun. 2002 Apr;70(4):2198-205. doi: 10.1128/IAI.70.4.2198-2205.2002. PMID:11895987 doi:http://dx.doi.org/10.1128/IAI.70.4.2198-2205.2002
- ↑ Sun J, Barbieri JT. Pseudomonas aeruginosa ExoT ADP-ribosylates CT10 regulator of kinase (Crk) proteins. J Biol Chem. 2003 Aug 29;278(35):32794-800. doi: 10.1074/jbc.M304290200. Epub , 2003 Jun 13. PMID:12807879 doi:http://dx.doi.org/10.1074/jbc.M304290200
- ↑ Garrity-Ryan L, Shafikhani S, Balachandran P, Nguyen L, Oza J, Jakobsen T, Sargent J, Fang X, Cordwell S, Matthay MA, Engel JN. The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities. Infect Immun. 2004 Jan;72(1):546-58. doi: 10.1128/IAI.72.1.546-558.2004. PMID:14688136 doi:http://dx.doi.org/10.1128/IAI.72.1.546-558.2004
- ↑ Wood S, Goldufsky J, Shafikhani SH. Pseudomonas aeruginosa ExoT Induces Atypical Anoikis Apoptosis in Target Host Cells by Transforming Crk Adaptor Protein into a Cytotoxin. PLoS Pathog. 2015 May 28;11(5):e1004934. doi: 10.1371/journal.ppat.1004934. , eCollection 2015 May. PMID:26020630 doi:http://dx.doi.org/10.1371/journal.ppat.1004934
- ↑ Wood SJ, Goldufsky JW, Bello D, Masood S, Shafikhani SH. Pseudomonas aeruginosa ExoT Induces Mitochondrial Apoptosis in Target Host Cells in a Manner That Depends on Its GTPase-activating Protein (GAP) Domain Activity. J Biol Chem. 2015 Nov 27;290(48):29063-73. doi: 10.1074/jbc.M115.689950. Epub , 2015 Oct 8. PMID:26451042 doi:http://dx.doi.org/10.1074/jbc.M115.689950
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