3vac | pdb_00003vac

Crystal Structure of the CFA/I Enterotoxigenic E. coli adhesin CfaE mutant G168D

spinqualitylabelsall models 3vac, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3vac is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CFAE_ECOLX Publication Abstract from PubMed CfaE, the tip adhesin of enterotoxigenic Escherichia coli colonization factor antigen I fimbriae, initiates binding of this enteropathogen to the small intestine. It comprises stacked beta-sandwich adhesin and pilin domains with the putative receptor-binding pocket at one pole and an equatorial interdomain interface. CfaE binding to erythrocytes is enhanced by application of moderate shear stress. A G168D replacement along the adhesin domain facing of the CfaE interdomain region was previously shown to decrease the dependence on shear by increasing binding at lower shear forces. To elucidate the structural basis for this functional change, we studied the properties of CfaE/G168D (with self-complemented donor strand), and solved its crystal structure at 2.6 A resolution. Compared to native CfaE, CfaE/G168D showed a downward shift in peak erythrocyte binding under shear stress and greater binding under static conditions. The thermal melting transition of CfaE/G168D occurred 10 degrees C below that of CfaE. Compared to CfaE, the atomic structure of CfaE/G168D revealed a 36% reduction in the buried surface area at the interdomain interface. Despite location of this single modification in the adhesin domain, CfaE/G168D exhibited structural derangements only in the adjoining pilin domain when compared to CfaE. In molecular dynamics simulations, the G168D mutation was associated with weakened interdomain interactions under tensile force. Taken together, these findings indicate that the adhesin and pilin domains of CfaE are conformationally tightly coupled and support the hypothesis that opening of the interface plays a critical modulatory role in the allosteric activation of CfaE. Tight Conformational Coupling between the Domains of the Enterotoxigenic Escherichia coli Fimbrial Adhesin CfaE Regulates Binding State Transition.,Liu Y, Esser L, Interlandi G, Kisiela DI, Tchesnokova V, Thomas WE, Sokurenko E, Xia D, Savarino SJ J Biol Chem. 2013 Feb 7. PMID:23393133 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Colonization factor antigen

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