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

abstract

  • 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.

published proceedings

  • EMBO J

altmetric score

  • 24

author list (cited authors)

  • Deivanayagam, C., Wann, E. R., Chen, W., Carson, M., Rajashankar, K. R., Hk, M., & Narayana, S.

citation count

  • 134

complete list of authors

  • Deivanayagam, Champion CS||Wann, Elisabeth R||Chen, Wei||Carson, Mike||Rajashankar, Kanagalaghatta R||Höök, Magnus||Narayana, Sthanam VL

publication date

  • December 2002

publisher