1he1

From Proteopedia

(Difference between revisions)

Revision as of 08:52, 10 January 2018

Crystal structure of the complex between the GAP domain of the Pseudomonas aeruginosa ExoS toxin and human Rac

Structural highlights

1he1 is a 4 chain structure with sequence from "bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	1e96, 1mh1, 1he9
Gene:	EXOS ("Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RAC1_HUMAN] Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion.^[1] ^[2] ^[3] ^[4] ^[5] Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.^[6] ^[7] ^[8] ^[9] ^[10]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Pseudomonas aeruginosa is an opportunistic bacterial pathogen. One of its major toxins, ExoS, is translocated into eukaryotic cells by a type III secretion pathway. ExoS is a dual function enzyme that affects two different Ras-related GTP binding proteins. The C-terminus inactivates Ras through ADP ribosylation, while the N-terminus inactivates Rho proteins through its GTPase activating protein (GAP) activity. Here we have determined the three-dimensional structure of a complex between Rac and the GAP domain of ExoS in the presence of GDP and AlF3. Composed of approximately 130 residues, this ExoS domain is the smallest GAP hitherto described. The GAP domain of ExoS is an all-helical protein with no obvious structural homology, and thus no recognizable evolutionary relationship, with the eukaryotic RhoGAP or RasGAP fold. Similar to other GAPs, ExoS downregulates Rac using an arginine finger to stabilize the transition state of the GTPase reaction, but the details of the ExoS-Rac interaction are unique. Considering the intrinsic resistance of P. aeruginosa to antibiotics, this might open up a new avenue towards blocking its pathogenicity.

How the Pseudomonas aeruginosa ExoS toxin downregulates Rac.,Wurtele M, Wolf E, Pederson KJ, Buchwald G, Ahmadian MR, Barbieri JT, Wittinghofer A Nat Struct Biol. 2001 Jan;8(1):23-6. PMID:11135665^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 1992 Aug 7;70(3):401-10. PMID:1643658
↑ Vincent S, Settleman J. The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. Mol Cell Biol. 1997 Apr;17(4):2247-56. PMID:9121475
↑ Bristow JM, Sellers MH, Majumdar D, Anderson B, Hu L, Webb DJ. The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin dynamics and thereby regulate cell migration. J Cell Sci. 2009 Dec 15;122(Pt 24):4535-46. doi: 10.1242/jcs.053728. Epub 2009, Nov 24. PMID:19934221 doi:10.1242/jcs.053728
↑ Hamill KJ, Hopkinson SB, DeBiase P, Jones JC. BPAG1e maintains keratinocyte polarity through beta4 integrin-mediated modulation of Rac1 and cofilin activities. Mol Biol Cell. 2009 Jun;20(12):2954-62. doi: 10.1091/mbc.E09-01-0051. Epub 2009, Apr 29. PMID:19403692 doi:10.1091/mbc.E09-01-0051
↑ Li X, Lee AY. Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through RhoGDIalpha-mediated inactivation of Rac1 GTPase. J Biol Chem. 2010 Oct 15;285(42):32436-45. doi: 10.1074/jbc.M110.120451. Epub, 2010 Aug 9. PMID:20696765 doi:10.1074/jbc.M110.120451
↑ Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 1992 Aug 7;70(3):401-10. PMID:1643658
↑ Vincent S, Settleman J. The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. Mol Cell Biol. 1997 Apr;17(4):2247-56. PMID:9121475
↑ Bristow JM, Sellers MH, Majumdar D, Anderson B, Hu L, Webb DJ. The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin dynamics and thereby regulate cell migration. J Cell Sci. 2009 Dec 15;122(Pt 24):4535-46. doi: 10.1242/jcs.053728. Epub 2009, Nov 24. PMID:19934221 doi:10.1242/jcs.053728
↑ Hamill KJ, Hopkinson SB, DeBiase P, Jones JC. BPAG1e maintains keratinocyte polarity through beta4 integrin-mediated modulation of Rac1 and cofilin activities. Mol Biol Cell. 2009 Jun;20(12):2954-62. doi: 10.1091/mbc.E09-01-0051. Epub 2009, Apr 29. PMID:19403692 doi:10.1091/mbc.E09-01-0051
↑ Li X, Lee AY. Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through RhoGDIalpha-mediated inactivation of Rac1 GTPase. J Biol Chem. 2010 Oct 15;285(42):32436-45. doi: 10.1074/jbc.M110.120451. Epub, 2010 Aug 9. PMID:20696765 doi:10.1074/jbc.M110.120451
↑ Wurtele M, Wolf E, Pederson KJ, Buchwald G, Ahmadian MR, Barbieri JT, Wittinghofer A. How the Pseudomonas aeruginosa ExoS toxin downregulates Rac. Nat Struct Biol. 2001 Jan;8(1):23-6. PMID:11135665 doi:http://dx.doi.org/10.1038/83007

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1he1"

@@ Line 1: / Line 1: @@
-==CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE GAP DOMAIN OF THE PSEUDOMONAS AERUGINOSA EXOS TOXIN AND HUMAN RAC==
+==Crystal structure of the complex between the GAP domain of the Pseudomonas aeruginosa ExoS toxin and human Rac==
 <StructureSection load='1he1' size='340' side='right' caption='[[1he1]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1e96|1e96]], [[1mh1|1mh1]], [[1he9|1he9]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EXOS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</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=1he1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1he1 OCA], [http://pdbe.org/1he1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1he1 RCSB], [http://www.ebi.ac.uk/pdbsum/1he1 PDBsum]</span></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=1he1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1he1 OCA], [http://pdbe.org/1he1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1he1 RCSB], [http://www.ebi.ac.uk/pdbsum/1he1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1he1 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/he/1he1_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/he/1he1_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 29: / Line 30: @@
 </div>
 <div class="pdbe-citations 1he1" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Exoenzyme|Exoenzyme]]
 == References ==
 <references/>

1he1

From Proteopedia

Revision as of 08:52, 10 January 2018

Crystal structure of the complex between the GAP domain of the Pseudomonas aeruginosa ExoS toxin and human Rac

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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