2vr3 | pdb_00002vr3

Structural and Biochemical Characterization of Fibrinogen binding to ClfA from Staphylocccus aureus

spinqualitylabelsall models 2vr3, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vr3 is a 4 chain structure with sequence from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CLFA_STAA8 Cell surface-associated protein implicated in virulence. Promotes bacterial attachment exclusively to the gamma-chain of human fibrinogen. Induces formation of bacterial clumps, which diminish the ability of group IIA phospholipase A2 to cause bacterial phospholipid hydrolysis and killing. Significantly decreases macrophage phagocytosis possibly thanks to the clumps, clumped bacteria being too large to be phagocytosed. Dominant factor responsible for human platelet aggregation, which may be an important mechanism for initiating infective endocarditis. Enhances spleen cell proliferative response in vitro, contributing significantly to the immunostimulatory activity of S.aureus. 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 The fibrinogen (Fg) binding MSCRAMM Clumping factor A (ClfA) from Staphylococcus aureus interacts with the C-terminal region of the fibrinogen (Fg) gamma-chain. ClfA is the major virulence factor responsible for the observed clumping of S. aureus in blood plasma and has been implicated as a virulence factor in a mouse model of septic arthritis and in rabbit and rat models of infective endocarditis. We report here a high-resolution crystal structure of the ClfA ligand binding segment in complex with a synthetic peptide mimicking the binding site in Fg. The residues in Fg required for binding to ClfA are identified from this structure and from complementing biochemical studies. Furthermore, the platelet integrin alpha(IIb)beta(3) and ClfA bind to the same segment in the Fg gamma-chain but the two cellular binding proteins recognize different residues in the common targeted Fg segment. Based on these differences, we have identified peptides that selectively antagonize the ClfA-Fg interaction. The ClfA-Fg binding mechanism is a variant of the "Dock, Lock and Latch" mechanism previously described for the Staphylococcus epidermidis SdrG-Fg interaction. The structural insights gained from analyzing the ClfANFg peptide complex and identifications of peptides that selectively recognize ClfA but not alpha(IIb)beta(3) may allow the design of novel anti-staphylococcal agents. Our results also suggest that different MSCRAMMs with similar structural organization may have originated from a common ancestor but have evolved to accommodate specific ligand structures. A structural model of the Staphylococcus aureus ClfA-fibrinogen interaction opens new avenues for the design of anti-staphylococcal therapeutics.,Ganesh VK, Rivera JJ, Smeds E, Ko YP, Bowden MG, Wann ER, Gurusiddappa S, Fitzgerald JR, Hook M PLoS Pathog. 2008 Nov;4(11):e1000226. Epub 2008 Nov 28. PMID:19043557 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Fibrinogen Fibrinogen binding protein

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