2JVH

Structure of C3-binding domain 4 of S. aureus protein Sbi

Summary for 2JVH

• Entry DOI: 10.2210/pdb2jvh/pdb
• Related: 2GOM 2JVG 2NOJ 2QFF
• Descriptor: IgG-binding protein SBI (1 entity in total)
• Functional Keywords: three helix bundle, immune system
• Biological source: Staphylococcus aureus
• Cellular location: Secreted (By similarity): Q99RL2
• Total number of polymer chains: 1
• Total formula weight: 8123.31

Authors

Upadhyay, A.,Burman, J.,Clark, E.A.,van den Elsen, J.M.H.,Bagby, S. (deposition date: 2007-09-20, release date: 2008-06-10, Last modification date: 2024-05-01)

Primary citation

Upadhyay, A.,Burman, J.D.,Clark, E.A.,Leung, E.,Isenman, D.E.,van den Elsen, J.M.,Bagby, S.
Structure-function analysis of the C3 binding region of Staphylococcus aureus immune subversion protein Sbi.
J.Biol.Chem., 283:22113-22120, 2008

PubMed Abstract: Among the recently discovered Staphylococcus aureus immune evasion proteins, Sbi is unique in its ability to interact with components of both the adaptive and innate immune systems of the host. Sbi domains I and II (Sbi-I and Sbi-II) bind IgG. Sbi domain IV (residues 198-266) binds the central complement protein C3. When linked to Sbi-III, Sbi-IV induces a futile consumption of complement via alternative pathway activation, whereas isolated Sbi-IV specifically inhibits the alternative pathway without complement consumption. Here we have determined the three-dimensional structure of Sbi-IV by NMR spectroscopy, showing that Sbi-IV adopts a three-helix bundle fold similar to those of the S. aureus complement inhibitors Efb-C, Ehp, and SCIN. The (1)H-(15)N HSQC spectrum of Sbi-III indicates that this domain, essential for futile complement consumption, is natively unfolded, at least when isolated from the rest of Sbi. Sbi-IV and Sbi-III-IV both bind C3dg with 1:1 stoichiometry and submicromolar affinity. Despite low overall sequence identity, Sbi possesses the same residues as Efb at two positions essential for Efb-C binding to C3d. Mutation to alanine of either of these residues, Arg-231 and Asn-238, abolishes both Sbi-IV binding to C3dg and Sbi-IV alternative pathway inhibition. The almost complete conservation of Sbi-III and Sbi-IV amino acid sequences across more than 30 strains isolated from human and animal hosts indicates that the unique mechanism of Sbi in complement system subversion is a feature of infections of both humans and economically important animals.

PubMed: 18550524
DOI: 10.1074/jbc.M802636200

Experimental method

SOLUTION NMR