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| Subject Categories: Structural Biology | Microbiology & Pathogens |
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| The EMBO Journal
(2002) 21, 6660–6672, doi: 10.1093/emboj/cdf619 |
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| A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A |
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| Champion C.S. Deivanayagam1, Elisabeth R. Wann2, 3, Wei Chen2, Mike Carson1, Kanagalaghatta R. Rajashankar4, Magnus Höök2 and Sthanam V.L. Narayana1 |
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1 Center for Biophysical Sciences and Engineering, School of Optometry, 244 CBSE, 1025 18th Street South, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA 2 Institute of Biosciences and Technology, Center for Extracellular Matrix Biology, 2121 West Holcombe Boulevard, Texas A&M University System Health Science Center, Houston, TX 77030-303, USA 3 Present address: Lexicon Genetics Inc., 8800 Technology Forest Place, The Woodlands, TX 77381, USA 4 Brookhaven National Laboratory, Building 725A-X9, Upton, NY 119773, USA To whom correspondence should be addressed Sthanam V.L. Narayana, narayana@uab.edu Received 8 April 2002; Revised 4 July 2002; Accepted 1 October 2002. |
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| Abstract |
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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  -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 408AGDV411 of the -chain, resulted in proteins with no or markedly reduced affinity for fibrinogen. |
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| Keywords: adhesins, clumping factor A, crystal structure, immunoglobulin fold, Staphylococcus aureus |
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