2011
DOI: 10.1016/j.molimm.2010.09.017
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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

Abstract: The structure of the complement-binding domain of Staphylococcus aureus protein Sbi (Sbi-IV) in complex with ligand C3d is presented. The 1.7 Å 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 inhib… Show more

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Cited by 27 publications
(40 citation statements)
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“…For example, Staphylococcus aureus secretes the highly cationic virulence factors EfbC and Ehp, which take advantage of the CR2 electrostatic “hot-spot” through the use of long-range, as well as short-range, electrostatic interactions (Supporting Figure S2A) [18]. Additionally, domain IV of the Staphylococcal immunoglobulin-binding protein (Sbi) targets the thioester side electrostatic “hot-spot” of C3d (Supporting Figure S2B), and in conjunction with Sbi domain III results in futile consumption of C3 through the formation of covalent adducts [19]. The electrostatic nature and binding sites of the Staphylococcus aureus virulence factors is further evidence for the key role of electrostatics in the function and evolution of complement C3d.…”
Section: Resultsmentioning
confidence: 99%
“…For example, Staphylococcus aureus secretes the highly cationic virulence factors EfbC and Ehp, which take advantage of the CR2 electrostatic “hot-spot” through the use of long-range, as well as short-range, electrostatic interactions (Supporting Figure S2A) [18]. Additionally, domain IV of the Staphylococcal immunoglobulin-binding protein (Sbi) targets the thioester side electrostatic “hot-spot” of C3d (Supporting Figure S2B), and in conjunction with Sbi domain III results in futile consumption of C3 through the formation of covalent adducts [19]. The electrostatic nature and binding sites of the Staphylococcus aureus virulence factors is further evidence for the key role of electrostatics in the function and evolution of complement C3d.…”
Section: Resultsmentioning
confidence: 99%
“…Many of the interactions observed at the interface, be they charged, polar, or apolar, conformed to mutagenesis data obtained previously (Clemenza and Isenman, 2000; Hannan et al, 2005; Isenman et al, 2010), or to mutagenesis experiments prompted by the new structure (van den Elsen and Isenman, 2011). Finally, the substantially overlapping contact areas on C3d observed among CR2(CCP1-2), Efb-C, and Sbi-IV in their respective co-crystal structures (Clark et al, 2011; Hammel et al, 2007; van den Elsen and Isenman, 2011) readily explains the competition of the staphylococcal immune evasion molecules for CR2 binding to C3d. Because of the nanomolar range affinity of Efb for C3d, compared with the μM range affinity of Sbi for C3d (Hammel et al, 2007; Upadhyay et al, 2008), the interaction of Efb with any C3d molecules that become covalently attached to the Staphylococcus aureus microbemay indeed be a physiologically relevant element through which this human pathogen evades antibody-mediated adaptive immunity (Ricklin et al, 2008).…”
Section: Co-crystal Structure Of the Cr2(ccp1-2):c3d Complexmentioning
confidence: 93%
“…Intriguingly, the secondary binding site for Sbi-IV on the convex surface of C3d revealed previously through X-ray crystallographic, NMR chemical shift perturbation 15 and SAXS analyses 8 , is located near the base or hinge region of the swapped C3d 17C α1 helix. It is at this position between helices α1 and α2 where Sbi-IV helix α1 forms strong interactions with the thioester cysteine C17/1010 and surrounding residues S15/1008 and Q20/1013 of C3d (Supplementary Figure S3 15 ).…”
Section: -20 Of Fh (Supplementarymentioning
confidence: 65%
“…Crystal structures have also shed light upon the molecular basis underlying the thioester-mediated attachment of C3d to antigenic surfaces 12 , provided explanations of how the interactions of C3d with its receptors (CR2 13 and CR3 14 ) facilitate the recognition of opsonised antigens, and the mechanisms by which pathogens such as Staphylococcus aureus utilise C3d-binding proteins (e.g. Sbi 15 , Efb-C 16,17 and Ecb/Ehp 18,19 ) to inhibit these interactions and evade the immune system. Furthermore, complexes of C3d with FH SCR domains 19 and 20 have been pivotal in understanding the regulatory measures in place to protect host tissues against the indiscriminate attachment of C3d to self versus non-self surfaces 20,21 .…”
Section: Introductionmentioning
confidence: 99%
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