2jol
From Proteopedia
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'''Average NMR structure of the catalytic domain of guanine nucleotide exchange factor BopE from Burkholderia pseudomallei''' | '''Average NMR structure of the catalytic domain of guanine nucleotide exchange factor BopE from Burkholderia pseudomallei''' | ||
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| + | ==Overview== | ||
| + | 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. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2JOL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Burkholderia_pseudomallei Burkholderia pseudomallei]. This structure supersedes the now removed PDB entry | + | 2JOL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Burkholderia_pseudomallei Burkholderia pseudomallei]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2aic 2aic]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JOL OCA]. |
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| + | ==Reference== | ||
| + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/18052936 18052936] | ||
[[Category: Burkholderia pseudomallei]] | [[Category: Burkholderia pseudomallei]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Williams, C.]] | [[Category: Williams, C.]] | ||
[[Category: Wu, H.]] | [[Category: Wu, H.]] | ||
| - | [[Category: | + | [[Category: Burkholderia pseudomallei]] |
| - | [[Category: | + | [[Category: Cell invasion]] |
| - | [[Category: | + | [[Category: Guanine nucleotide exchange factor]] |
| - | [[Category: | + | [[Category: Signaling protein]] |
| - | [[Category: | + | [[Category: Sope]] |
| - | + | [[Category: Sope2]] | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | [[Category: Type iii secretion]] |
| + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:28:08 2008'' | ||
Revision as of 10:28, 30 April 2008
Average NMR structure of the catalytic domain of guanine nucleotide exchange factor BopE from Burkholderia pseudomallei
Overview
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.
About this Structure
2JOL is a Single protein structure of sequence from Burkholderia pseudomallei. This structure supersedes the now removed PDB entry 2aic. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Wed Apr 30 13:28:08 2008
