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

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 γ-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 γ-chain, resulted in proteins with no or markedly reduced affinity for fibrinogen.
  • Published In

  • EMBO Journal  Journal
  • Digital Object Identifier (doi)

    Author List

  • Deivanayagam CCS; Wann ER; Chen W; Carson M; Rajashankar KR; Höök M; Narayana SVL
  • Start Page

  • 6660
  • End Page

  • 6672
  • Volume

  • 21
  • Issue

  • 24