2VR3

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

Summary for 2VR3

• Entry DOI: 10.2210/pdb2vr3/pdb
• Related: 1DUG 1FIB 1FIC 1FID 1FZA 1FZB 1FZC 1FZE 1FZF 1FZG 1LT9 1LTJ 1N86 1N8E 1RE3 1RE4 1RF0 1RF1 2FFD 2FIB 3FIB
• Descriptor: CLUMPING FACTOR A, FIBRINOGEN GAMMA-CHAIN (3 entities in total)
• Functional Keywords: platelet aggregation, peptidoglycan-anchor, cell adhesion, staphylococcus aureus, fibrinogen gamma-chain, secreted, cell wall, virulence, clumping factor
• Biological source: STAPHYLOCOCCUS AUREUS; More
• Cellular location: Secreted, cell wall; Peptidoglycan-anchor (Potential): Q2G015; Secreted: P02679
• Total number of polymer chains: 4
• Total formula weight: 74155.80

Authors

Ganesh, V.K.,Rivera, J.J.,Smeds, E.,Bowden, M.G.,Wann, E.R.,Gurusidappa, S.,Fitzgerald, J.R.,Hook, M. (deposition date: 2008-03-25, release date: 2009-05-19, Last modification date: 2024-11-20)

Primary citation

Ganesh, V.K.,Rivera, J.J.,Smeds, E.,Ko, Y.P.,Bowden, M.G.,Wann, E.R.,Gurusiddappa, S.,Fitzgerald, J.R.,Hook, M.
A Structural Model of the Staphylococcus Aureus Clfa-Fibrinogen Interaction Opens New Avenues for the Design of Anti-Staphylococcal Therapeutics.
Plos Pathog., 4:226-, 2008

PubMed 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.

PubMed: 19043557
DOI: 10.1371/JOURNAL.PPAT.1000226

Experimental method

X-RAY DIFFRACTION (1.95 Å)