View source for 2jol

[[Image:2jol.gif|left|200px]]

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{{STRUCTURE_2jol|  PDB=2jol  |  SCENE=  }} 

'''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 [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]. 

==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: Single protein]]
[[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: Cell invasion]]
[[Category: Guanine nucleotide exchange factor]]
[[Category: Signaling protein]]
[[Category: Sope]]
[[Category: Sope2]]
[[Category: Type iii secretion]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:28:08 2008''