A structural basis for complement inhibition by Staphylococcus aureus

Nat Immunol. 2007 Apr;8(4):430-7. doi: 10.1038/ni1450. Epub 2007 Mar 11.


To provide insight into bacterial suppression of complement-mediated immunity, we present here structures of a bacterial complement inhibitory protein, both free and bound to its complement target. The 1.25-A structure of the complement component C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) demonstrated a helical motif involved in complement regulation, whereas the 2.2-A structure of Efb-C bound to the C3d domain of human C3 allowed insight into the recognition of complement proteins by invading pathogens. Our structure-function studies provided evidence for a previously unrecognized mode of complement inhibition whereby Efb-C binds to native C3 and alters the solution conformation of C3 in a way that renders it unable to participate in successful 'downstream' activation of the complement response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / immunology*
  • Calorimetry
  • Complement C3 / antagonists & inhibitors*
  • Complement C3 / chemistry
  • Complement C3 / immunology
  • Crystallography, X-Ray
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Models, Molecular
  • Protein Conformation
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / chemistry
  • Staphylococcus aureus / immunology*
  • Surface Plasmon Resonance


  • Bacterial Proteins
  • Complement C3
  • Efb protein, Staphylococcus aureus

Associated data

  • PDB/2GOM
  • PDB/2GOX