|
|
| Line 1: |
Line 1: |
| | | | |
| | ==NMR structure of the catalytic domain of guanine nucleotide exchange factor BopE from Burkholderia pseudomallei== | | ==NMR structure of the catalytic domain of guanine nucleotide exchange factor BopE from Burkholderia pseudomallei== |
| - | <StructureSection load='2jok' size='340' side='right'caption='[[2jok]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2jok' size='340' side='right'caption='[[2jok]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jok]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_pseudomallei"_whitmore_1913 "bacillus pseudomallei" whitmore 1913]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JOK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jok]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei Burkholderia pseudomallei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JOK FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1r6e|1r6e]], [[1r9k|1r9k]], [[1gzs|1gzs]], [[2jol|2jol]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bopE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28450 "Bacillus pseudomallei" Whitmore 1913])</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=2jok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jok OCA], [https://pdbe.org/2jok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jok RCSB], [https://www.ebi.ac.uk/pdbsum/2jok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jok 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=2jok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jok OCA], [https://pdbe.org/2jok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jok RCSB], [https://www.ebi.ac.uk/pdbsum/2jok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jok ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/BOPE_BURPS BOPE_BURPS]] Activator for both CDC42 and RAC1 by directly interacting with these Rho GTPases and acting as a guanine nucleotide exchange factor (GEF). This activation results in actin cytoskeleton rearrangements and stimulates membrane ruffling, thus promoting bacterial entry into non-phagocytic cells.<ref>PMID:12410823</ref> <ref>PMID:12897019</ref> <ref>PMID:15289563</ref>
| + | [https://www.uniprot.org/uniprot/BOPE_BURPS BOPE_BURPS] Activator for both CDC42 and RAC1 by directly interacting with these Rho GTPases and acting as a guanine nucleotide exchange factor (GEF). This activation results in actin cytoskeleton rearrangements and stimulates membrane ruffling, thus promoting bacterial entry into non-phagocytic cells.<ref>PMID:12410823</ref> <ref>PMID:12897019</ref> <ref>PMID:15289563</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 33: |
Line 32: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus pseudomallei whitmore 1913]] | |
| - | [[Category: Large Structures]] | |
| - | [[Category: Bagby, S]] | |
| - | [[Category: Elsen, J M.H van den]] | |
| - | [[Category: Galyov, E E]] | |
| - | [[Category: Upadhyay, A]] | |
| - | [[Category: Williams, C]] | |
| - | [[Category: Wu, H]] | |
| | [[Category: Burkholderia pseudomallei]] | | [[Category: Burkholderia pseudomallei]] |
| - | [[Category: Cell invasion]] | + | [[Category: Large Structures]] |
| - | [[Category: Guanine nucleotide exchange factor]] | + | [[Category: Bagby S]] |
| - | [[Category: Signaling protein]] | + | [[Category: Galyov EE]] |
| - | [[Category: Sope]] | + | [[Category: Upadhyay A]] |
| - | [[Category: Sope2]] | + | [[Category: Williams C]] |
| - | [[Category: Type iii secretion]] | + | [[Category: Wu H]] |
| | + | [[Category: Van den Elsen JMH]] |
| Structural highlights
Function
BOPE_BURPS Activator for both CDC42 and RAC1 by directly interacting with these Rho GTPases and acting as a guanine nucleotide exchange factor (GEF). This activation results in actin cytoskeleton rearrangements and stimulates membrane ruffling, thus promoting bacterial entry into non-phagocytic cells.[1] [2] [3]
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
BopE is a type III secreted protein from Burkholderia pseudomallei, the aetiological agent of melioidosis, a severe emerging infection. BopE is a GEF (guanine-nucleotide-exchange factor) for the Rho GTPases Cdc42 (cell division cycle 42) and Rac1. We have determined the structure of BopE catalytic domain (amino acids 78-261) by NMR spectroscopy and it shows that BopE(78-261) comprises two three-helix bundles (alpha1alpha4alpha5 and alpha2alpha3alpha6). This fold is similar to that adopted by the BopE homologues SopE and SopE2, which are GEFs from Salmonella. Whereas the two three-helix bundles of SopE(78-240) and SopE2(69-240) form the arms of a 'Lambda' shape, BopE(78-261) adopts a more closed conformation with substantial interactions between the two three-helix bundles. We propose that arginine and proline residues are important in the conformational differences between BopE and SopE/E2. Analysis of the molecular interface in the SopE(78-240)-Cdc42 complex crystal structure indicates that, in a BopE-Cdc42 interaction, the closed conformation of BopE(78-261) would engender steric clashes with the Cdc42 switch regions. This implies that BopE(78-261) must undergo a closed-to-open conformational change in order to catalyse guanine nucleotide exchange. In an NMR titration to investigate the BopE(78-261)-Cdc42 interaction, the appearance of additional peaks per NH for residues in hinge regions of BopE(78-261) indicates that BopE(78-261) does undergo a closed-to-open conformational change in the presence of Cdc42. The conformational change hypothesis is further supported by substantial improvement of BopE(78-261) catalytic efficiency through mutations that favour an open conformation. Requirement for closed-to-open conformational change explains the 10-40-fold lower k(cat) of BopE compared with SopE and SopE2.
The guanine-nucleotide-exchange factor BopE from Burkholderia pseudomallei adopts a compact version of the Salmonella SopE/SopE2 fold and undergoes a closed-to-open conformational change upon interaction with Cdc42.,Upadhyay A, Wu HL, Williams C, Field T, Galyov EE, van den Elsen JM, Bagby S Biochem J. 2008 May 1;411(3):485-93. PMID:18052936[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stevens MP, Wood MW, Taylor LA, Monaghan P, Hawes P, Jones PW, Wallis TS, Galyov EE. An Inv/Mxi-Spa-like type III protein secretion system in Burkholderia pseudomallei modulates intracellular behaviour of the pathogen. Mol Microbiol. 2002 Nov;46(3):649-59. PMID:12410823
- ↑ Stevens MP, Friebel A, Taylor LA, Wood MW, Brown PJ, Hardt WD, Galyov EE. A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity. J Bacteriol. 2003 Aug;185(16):4992-6. PMID:12897019
- ↑ Stevens MP, Haque A, Atkins T, Hill J, Wood MW, Easton A, Nelson M, Underwood-Fowler C, Titball RW, Bancroft GJ, Galyov EE. Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis. Microbiology. 2004 Aug;150(Pt 8):2669-76. PMID:15289563 doi:10.1099/mic.0.27146-0
- ↑ Upadhyay A, Wu HL, Williams C, Field T, Galyov EE, van den Elsen JM, Bagby S. The guanine-nucleotide-exchange factor BopE from Burkholderia pseudomallei adopts a compact version of the Salmonella SopE/SopE2 fold and undergoes a closed-to-open conformational change upon interaction with Cdc42. Biochem J. 2008 May 1;411(3):485-93. PMID:18052936 doi:10.1042/BJ20071546
|
