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4f27

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Revision as of 13:37, 11 August 2016

Crystal structures reveal the multi-ligand binding mechanism of the Staphylococcus aureus ClfB

Structural highlights

4f27 is a 2 chain structure with sequence from Staar. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	4f1z, 4f20, 4f24
Gene:	clfB, SAR2709 (STAAR)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FIBA_HUMAN] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=The majority of cases of afibrinogenemia are due to truncating mutations. Variations in position Arg-35 (the site of cleavage of fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias. Defects in FGA are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.^[1]

Function

[CLFB_STAAR] Cell surface-associated protein implicated in virulence by promoting bacterial attachment to both alpha- and beta-chains of human fibrinogen and inducing the formation of bacterial clumps. [FIBA_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.

Publication Abstract from PubMed

Staphylococcus aureus (S. aureus) pathogenesis is a complex process involving a diverse array of extracellular and cell wall components. ClfB, an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family surface protein, described as a fibrinogen-binding clumping factor, is a key determinant of S. aureus nasal colonization, but the molecular basis for ClfB-ligand recognition remains unknown. In this study, we solved the crystal structures of apo-ClfB and its complexes with fibrinogen alpha (Fg alpha) and cytokeratin 10 (CK10) peptides. Structural comparison revealed a conserved glycine-serine-rich (GSR) ClfB binding motif (GSSGXGXXG) within the ligands, which was also found in other human proteins such as Engrailed protein, TCF20 and Dermokine proteins. Interaction between Dermokine and ClfB was confirmed by subsequent binding assays. The crystal structure of ClfB complexed with a 15-residue peptide derived from Dermokine revealed the same peptide binding mode of ClfB as identified in the crystal structures of ClfB-Fg alpha and ClfB-CK10. The results presented here highlight the multi-ligand binding property of ClfB, which is very distinct from other characterized MSCRAMMs to-date. The adherence of multiple peptides carrying the GSR motif into the same pocket in ClfB is reminiscent of MHC molecules. Our results provide a template for the identification of other molecules targeted by S. aureus during its colonization and infection. We propose that other MSCRAMMs like ClfA and SdrG also possess multi-ligand binding properties.

Crystal Structures Reveal the Multi-Ligand Binding Mechanism of Staphylococcus aureus ClfB.,Xiang H, Feng Y, Wang J, Liu B, Chen Y, Liu L, Deng X, Yang M PLoS Pathog. 2012 Jun;8(6):e1002751. Epub 2012 Jun 14. PMID:22719251^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Nat Genet. 1993 Mar;3(3):252-5. PMID:8097946 doi:http://dx.doi.org/10.1038/ng0393-252
↑ Xiang H, Feng Y, Wang J, Liu B, Chen Y, Liu L, Deng X, Yang M. Crystal Structures Reveal the Multi-Ligand Binding Mechanism of Staphylococcus aureus ClfB. PLoS Pathog. 2012 Jun;8(6):e1002751. Epub 2012 Jun 14. PMID:22719251 doi:10.1371/journal.ppat.1002751

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4f27"

@@ Line 1: / Line 1: @@
 ==Crystal structures reveal the multi-ligand binding mechanism of the Staphylococcus aureus ClfB==
 <StructureSection load='4f27' size='340' side='right' caption='[[4f27]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f1z|4f1z]], [[4f20|4f20]], [[4f24|4f24]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">clfB, SAR2709 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=282458 STAAR])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4f27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f27 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4f27 RCSB], [http://www.ebi.ac.uk/pdbsum/4f27 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4f27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f27 OCA], [http://pdbe.org/4f27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f27 RCSB], [http://www.ebi.ac.uk/pdbsum/4f27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f27 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4f27" style="background-color:#fffaf0;"></div>
 ==See Also==

4f27

From Proteopedia

Revision as of 13:37, 11 August 2016

Crystal structures reveal the multi-ligand binding mechanism of the Staphylococcus aureus ClfB

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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