A structural basis for Staphylococcal complement subversion: X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d.
The structure of the complement-binding domain of Staphylococcus aureus protein Sbi (Sbi-IV) in complex with ligand C3d is presented. The 1.7Å resolution structure reveals the molecular details of the recognition of thioester-containing fragment C3d of the central complement component C3, involving interactions between residues of Sbi-IV helix α2 and the acidic concave surface of C3d. The complex provides a structural basis for the binding preference of Sbi for native C3 over C3b and explains how Sbi-IV inhibits the interaction between C3d and complement receptor 2. A second C3d binding site on Sbi-IV is identified in the crystal structure that is not observed in related S. aureus C3 inhibitors Efb-C and Ehp. This binding mode perhaps hints as to how Sbi-IV, as part of Sbi, forms a C3b-Sbi adduct and causes futile consumption of C3, an extraordinary aspect of Sbi function that is not shared by any other known Staphylococcal complement inhibitor.
University of Bath, Department of Biology and Biochemistry, Claverton Down, Bath BA2 7AY, United Kingdom.
Elizabeth A
EA
Clark
Susan
S
Crennell
Abhishek
A
Upadhyay
Alexey V
AV
Zozulya
Julia D
JD
Mackay
Dmitri I
DI
Svergun
Stefan
S
Bagby
Jean M H
JM
van den Elsen
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology*; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology*; D015933:Complement C3d / Q000737:chemistry* / Q000276:immunology*; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D013211:Staphylococcus aureus / Q000276:immunology*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D017186:Titrimetry
D000596:Amino Acids; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008024:Ligands; C112405:Sbi protein, Staphylococcus aureus; D015933:Complement C3d