A structural basis for complement inhibition by Staphylococcus aureus

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-angstrom 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-angstrom 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.