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  • The EMBO Journal (2002) 21, 6660 - 6672
  • doi:10.1093/emboj/cdf619

A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A

Champion C.S. Deivanayagam1, Elisabeth R. Wann2,3, Wei Chen2, Mike Carson1, Kanagalaghatta R. Rajashankar4, Magnus Höök2 and Sthanam V.L. Narayana1

  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

Correspondence to:

Sthanam V.L. Narayana, E-mail: narayana@uab.edu

Received 8 April 2002; Accepted 1 October 2002; Revised 4 July 2002

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 408AGDV411 of the gamma-chain, resulted in proteins with no or markedly reduced affinity for fibrinogen.

  • Keywords:

    • adhesins,
    • clumping factor A,
    • crystal structure,
    • immunoglobulin fold,
    • Staphylococcus aureus