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| {{STRUCTURE_2jol| PDB=2jol | SCENE= }} | | {{STRUCTURE_2jol| PDB=2jol | SCENE= }} |
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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==
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| 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.
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| | {{ABSTRACT_PUBMED_18052936}} |
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| ==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 [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]. | | 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 experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JOL OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Sope2]] | | [[Category: Sope2]] |
| [[Category: Type iii secretion]] | | [[Category: Type iii secretion]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:28:08 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 16:18:05 2008'' |