Structural highlights
Function
[CLFA_STAAE] 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.[1] [2] [3] [4]
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
We report here the crystal structure of the minimal ligand-binding segment of the Staphylococcus aureus MSCRAMM, clumping factor A. This fibrinogen-binding segment contains two similarly folded domains. The fold observed is a new variant of the immunoglobulin motif that we have called DE-variant or the DEv-IgG fold. This subgroup includes the ligand-binding domain of the collagen-binding S.aureus MSCRAMM CNA, and many other structures previously classified as jelly rolls. Structure predictions suggest that the four fibrinogen-binding S.aureus MSCRAMMs identified so far would also contain the same DEv-IgG fold. A systematic docking search using the C-terminal region of the fibrinogen gamma-chain as a probe suggested that a hydrophobic pocket formed between the two DEv-IgG domains of the clumping factor as the ligand-binding site. Mutagenic substitution of residues Tyr256, Pro336, Tyr338 and Lys389 in the clumping factor, which are proposed to contact the terminal residues (408)AGDV(411) of the gamma-chain, resulted in proteins with no or markedly reduced affinity for fibrinogen.
A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A.,Deivanayagam CC, Wann ER, Chen W, Carson M, Rajashankar KR, Hook M, Narayana SV EMBO J. 2002 Dec 16;21(24):6660-72. PMID:12485987[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dominiecki ME, Weiss J. Antibacterial action of extracellular mammalian group IIA phospholipase A2 against grossly clumped Staphylococcus aureus. Infect Immun. 1999 May;67(5):2299-305. PMID:10225887
- ↑ Siboo IR, Cheung AL, Bayer AS, Sullam PM. Clumping factor A mediates binding of Staphylococcus aureus to human platelets. Infect Immun. 2001 May;69(5):3120-7. PMID:11292731 doi:http://dx.doi.org/10.1128/IAI.69.5.3120-3127.2001
- ↑ O'Brien L, Kerrigan SW, Kaw G, Hogan M, Penades J, Litt D, Fitzgerald DJ, Foster TJ, Cox D. Multiple mechanisms for the activation of human platelet aggregation by Staphylococcus aureus: roles for the clumping factors ClfA and ClfB, the serine-aspartate repeat protein SdrE and protein A. Mol Microbiol. 2002 May;44(4):1033-44. PMID:12010496
- ↑ Palmqvist N, Patti JM, Tarkowski A, Josefsson E. Expression of staphylococcal clumping factor A impedes macrophage phagocytosis. Microbes Infect. 2004 Feb;6(2):188-95. PMID:14998517 doi:http://dx.doi.org/10.1016/j.micinf.2003.11.005
- ↑ Deivanayagam CC, Wann ER, Chen W, Carson M, Rajashankar KR, Hook M, Narayana SV. A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A. EMBO J. 2002 Dec 16;21(24):6660-72. PMID:12485987
