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 Deivanayagam, Elisabeth R. Wann, Wei Chen, Mike Carson, Kanagalaghatta R. Rajashankar, Magnus Höök, Sthanam V L Narayana

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6660-6672
Number of pages13
JournalEMBO Journal
Volume21
Issue number24
DOIs
StatePublished - Dec 16 2002

Keywords

  • Adhesins
  • Clumping factor A
  • Crystal structure
  • Immunoglobulin fold
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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