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

EMBO J. 2002 Dec 16;21(24):6660-72. doi: 10.1093/emboj/cdf619.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adhesins, Bacterial / chemistry*
  • Amino Acid Sequence
  • Binding Sites
  • Circular Dichroism
  • Crystallography, X-Ray
  • DNA Mutational Analysis
  • Dose-Response Relationship, Drug
  • Fibrinogen / metabolism
  • Immunoglobulins / metabolism
  • Lysine / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Mutagenesis, Site-Directed
  • Proline / chemistry
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins
  • Sequence Homology, Amino Acid
  • Staphylococcus aureus / metabolism*
  • Tyrosine / chemistry

Substances

  • Adhesins, Bacterial
  • Immunoglobulins
  • Recombinant Proteins
  • Tyrosine
  • Fibrinogen
  • Proline
  • Lysine

Associated data

  • PDB/1N67