title: A structural basis for complement inhibition by Staphylococcus aureus.
abstract: 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.
authors.affiliation: Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri at Kansas City, Kansas City, Missouri 64110, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Hammel
authors.forename: Georgia
authors.initials: G
authors.lastname: Sfyroera
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricklin
authors.forename: Paola
authors.initials: P
authors.lastname: Magotti
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Brian V
authors.initials: BV
authors.lastname: Geisbrecht
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D002151:Calorimetry; D003176:Complement C3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D018360:Crystallography, X-Ray; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology*; D020349:Surface Plasmon Resonance
chemical_list: D001426:Bacterial Proteins; D003176:Complement C3; C114014:Efb protein, Staphylococcus aureus