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PDBsum entry 2vr3

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protein Protein-protein interface(s) links
Cell adhesion PDB id
2vr3
Jmol
Contents
Protein chains
308 a.a. *
12 a.a. *
13 a.a. *
Waters ×527
* Residue conservation analysis
PDB id:
2vr3
Name: Cell adhesion
Title: Structural and biochemical characterization of fibrinogen binding to clfa from staphylocccus aureus
Structure: Clumping factor a. Chain: a, b. Fragment: n2n3, residues 229-545. Synonym: fibrinogen-binding protein a, fibrinogen receptor a. Engineered: yes. Mutation: yes. Other_details: engineered disulfide bond between 327 and 541.
Source: Staphylococcus aureus. Organism_taxid: 1280. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606
Resolution:
1.95Å     R-factor:   0.212     R-free:   0.279
Authors: V.K.Ganesh,J.J.Rivera,E.Smeds,M.G.Bowden,E.R.Wann, S.Gurusidappa,J.R.Fitzgerald,M.Hook
Key ref: V.K.Ganesh et al. (2008). A structural model of the Staphylococcus aureus ClfA-fibrinogen interaction opens new avenues for the design of anti-staphylococcal therapeutics. PLoS Pathog, 4, e1000226. PubMed id: 19043557
Date:
25-Mar-08     Release date:   19-May-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q2G015  (CLFA_STAA8) -  Clumping factor A
Seq:
Struc:
 
Seq:
Struc:
927 a.a.
308 a.a.*
Protein chain
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
Seq:
Struc:
453 a.a.
12 a.a.*
Protein chain
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
Seq:
Struc:
453 a.a.
13 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cell wall   1 term 
  Biological process     cell adhesion   1 term 

 

 
PLoS Pathog 4:e1000226 (2008)
PubMed id: 19043557  
 
 
A structural model of the Staphylococcus aureus ClfA-fibrinogen interaction opens new avenues for the design of anti-staphylococcal therapeutics.
V.K.Ganesh, J.J.Rivera, E.Smeds, Y.P.Ko, M.G.Bowden, E.R.Wann, S.Gurusiddappa, J.R.Fitzgerald, M.Höök.
 
  ABSTRACT  
 
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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21208192 A.Ruggiero, F.Squeglia, D.Marasco, R.Marchetti, A.Molinaro, and R.Berisio (2011).
X-ray structural studies of the entire extracellular region of the serine/threonine kinase PrkC from Staphylococcus aureus.
  Biochem J, 435, 33-41.
PDB code: 3py9
21280131 E.Matsuoka, Y.Tanaka, M.Kuroda, Y.Shouji, T.Ohta, I.Tanaka, and M.Yao (2011).
Crystal structure of the functional region of Uro-adherence factor A from Staphylococcus saprophyticus reveals participation of the B domain in ligand binding.
  Protein Sci, 20, 406-416.  
21347378 H.A.Choy, M.M.Kelley, J.Croda, J.Matsunaga, J.T.Babbitt, A.I.Ko, M.Picardeau, and D.A.Haake (2011).
The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans.
  PLoS One, 6, e16879.  
21404359 K.Vengadesan, and S.V.Narayana (2011).
Structural biology of Gram-positive bacterial adhesins.
  Protein Sci, 20, 759-772.  
20550675 A.J.McCarthy, and J.A.Lindsay (2010).
Genetic variation in Staphylococcus aureus surface and immune evasion genes is lineage associated: implications for vaccine design and host-pathogen interactions.
  BMC Microbiol, 10, 173.  
20090838 E.M.Barbu, V.K.Ganesh, S.Gurusiddappa, R.C.Mackenzie, T.J.Foster, T.C.Sudhof, and M.Höök (2010).
beta-Neurexin is a ligand for the Staphylococcus aureus MSCRAMM SdrC.
  PLoS Pathog, 6, e1000726.  
20515471 F.M.Burke, N.McCormack, S.Rindi, P.Speziale, and T.J.Foster (2010).
Fibronectin-binding protein B variation in Staphylococcus aureus.
  BMC Microbiol, 10, 160.  
20714354 H.S.Seo, Y.Q.Xiong, J.Mitchell, R.Seepersaud, A.S.Bayer, and P.M.Sullam (2010).
Bacteriophage lysin mediates the binding of streptococcus mitis to human platelets through interaction with fibrinogen.
  PLoS Pathog, 6, 0.  
20007717 J.A.Geoghegan, V.K.Ganesh, E.Smeds, X.Liang, M.Höök, and T.J.Foster (2010).
Molecular characterization of the interaction of staphylococcal microbial surface components recognizing adhesive matrix molecules (MSCRAMM) ClfA and Fbl with fibrinogen.
  J Biol Chem, 285, 6208-6216.  
20584910 S.Ramboarina, J.A.Garnett, M.Zhou, Y.Li, Z.Peng, J.D.Taylor, W.C.Lee, A.Bodey, J.W.Murray, Y.Alguel, J.Bergeron, B.Bardiaux, E.Sawyer, R.Isaacson, C.Tagliaferri, E.Cota, M.Nilges, P.Simpson, T.Ruiz, H.Wu, and S.Matthews (2010).
Structural insights into serine-rich fimbriae from Gram-positive bacteria.
  J Biol Chem, 285, 32446-32457.
PDB codes: 2kub 2x12
19527885 K.A.Kline, S.Fälker, S.Dahlberg, S.Normark, and B.Henriques-Normark (2009).
Bacterial adhesins in host-microbe interactions.
  Cell Host Microbe, 5, 580-592.  
19303408 K.Sivaraman, and A.M.Cole (2009).
Pathogenesis gene families in the common minimal genome of Staphylococcus aureus are hypervariable.
  FEBS Lett, 583, 1304-1308.  
19995192 P.Speziale, G.Pietrocola, S.Rindi, M.Provenzano, G.Provenza, A.Di Poto, L.Visai, and C.R.Arciola (2009).
Structural and functional role of Staphylococcus aureus surface components recognizing adhesive matrix molecules of the host.
  Future Microbiol, 4, 1337-1352.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.