2vr3
From Proteopedia
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| - | {{STRUCTURE_2vr3| PDB=2vr3 | SCENE= }} | ||
| - | ===STRUCTURAL AND BIOCHEMICAL CHARACTERIZATION OF FIBRINOGEN BINDING TO CLFA FROM STAPHYLOCCCUS AUREUS=== | ||
| - | {{ABSTRACT_PUBMED_19043557}} | ||
| - | == | + | ==Structural and Biochemical Characterization of Fibrinogen binding to ClfA from Staphylocccus aureus== |
| - | [[ | + | <StructureSection load='2vr3' size='340' side='right'caption='[[2vr3]], [[Resolution|resolution]] 1.95Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2vr3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VR3 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vr3 OCA], [https://pdbe.org/2vr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vr3 RCSB], [https://www.ebi.ac.uk/pdbsum/2vr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vr3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CLFA_STAA8 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.<ref>PMID:10225887</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vr/2vr3_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vr3 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:19043557</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 2vr3" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Fibrinogen|Fibrinogen]] | *[[Fibrinogen|Fibrinogen]] | ||
*[[Fibrinogen binding protein|Fibrinogen binding protein]] | *[[Fibrinogen binding protein|Fibrinogen binding protein]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| - | [[Category: | + | </StructureSection> |
| - | + | [[Category: Homo sapiens]] | |
| - | + | [[Category: Large Structures]] | |
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[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
| - | [[Category: | + | [[Category: Bowden MG]] |
| + | [[Category: Fitzgerald JR]] | ||
| + | [[Category: Ganesh VK]] | ||
| + | [[Category: Gurusidappa S]] | ||
| + | [[Category: Hook M]] | ||
| + | [[Category: Rivera JJ]] | ||
| + | [[Category: Smeds E]] | ||
| + | [[Category: Wann ER]] | ||
Current revision
Structural and Biochemical Characterization of Fibrinogen binding to ClfA from Staphylocccus aureus
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