Identification of an amino acid signature sequence predictive of protein G-inhibitable IgG3-binding activity in group-A streptococcal IgG-binding proteins

Pack, Todd D.; Podbielski, Andreas; Boyle, Michael D. P.

doi:10.1016/0378-1119(96)00102-3

Cited by 13 publications

(9 citation statements)

References 21 publications

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“…M18 strains have no mrp18 gene, as it was previously reported (13). Enn18 has been reported to bind human IgG3, but its role in interaction with complement regulatory proteins has not been studied (31).…”

Section: Resultsmentioning

confidence: 92%

Interaction between Complement Regulators andStreptococcus pyogenes: Binding of C4b-Binding Protein and Factor H/Factor H-Like Protein 1 to M18 Strains Involves Two Different Cell Surface Molecules

Pérez-Caballero

García-Laorden

Cortés

et al. 2004

The Journal of Immunology

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Streptococcus pyogenes, or group A Streptococcus, is one of the most frequent causes of pharyngitis and skin infections in humans. Many virulence mechanisms have been suggested to be involved in the infectious process. Among them is the binding to the bacterial cell surface of the complement regulatory proteins factor H, factor H-like protein 1 (FHL-1), and C4b-binding protein. Previous studies indicate that binding of these three regulators to the streptococcal cell involves the M protein encoded by the emm gene. M-type 18 strains are prevalent among clinical isolates and have been shown to interact with all three complement regulators simultaneously. Using isogenic strains lacking expression of the Emm18 or the Enn18 proteins, we demonstrate in this study that, in contradistinction to previously described S. pyogenes strains, M18 strains bind the complement regulators factor H, FHL-1, and C4b-binding protein through two distinct cell surface proteins. Factor H and FHL-1 bind to the Emm18 protein, while C4BP binds to the Enn18 protein. We propose that expression of two distinct surface structures that bind complement regulatory proteins represents a unique adaptation of M18 strains that enhances their resistance to opsonization by human plasma and increases survival of this particular S. pyogenes strain in the human host. These new findings illustrate that S. pyogenes has evolved diverse mechanisms for recruitment of complement regulatory proteins to the bacterial surface to evade immune clearance in the human host.

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Section: Resultsmentioning

confidence: 92%

Interaction between Complement Regulators andStreptococcus pyogenes: Binding of C4b-Binding Protein and Factor H/Factor H-Like Protein 1 to M18 Strains Involves Two Different Cell Surface Molecules

Pérez-Caballero

García-Laorden

Cortés

et al. 2004

The Journal of Immunology

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“…FgBP does not show homology to the proposed EQ-rich IgG3-and IgG1234-binding domains present in the class II group of M proteins and protein H of S. pyogenes (Bessen et al, 1997;Pack et al, 1996), nor does it show sequence homology to the IgG-binding domains of protein A or protein G. Despite the fact that all three proteins possess (some) a-helical structure in their binding domains, available evidence indicates that the strategy used by FgBP for binding IgG-Fc differs from the mode of interaction adopted by protein A and protein G. However, competition ELISAs and site-directed mutagenesis studies show that the FgBP-binding site on IgG overlaps with the binding sites of protein A and protein G and involves residues in the Leu251-Ser254 and Leu432-Tyr436 loops of IgG that interact with protein A and/or protein G (Lewis et al, 2008a). It is known that acidic and charged residues play important roles in the interaction between protein A/G and IgG-Fc (Sauer-Eriksson et al, 1995).…”

Section: Resultsmentioning

confidence: 96%

Localization of the equine IgG-binding domain in the fibrinogen-binding protein (FgBP) of Streptococcus equi subsp. equi

et al. 2009

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Fibrinogen-binding protein (FgBP, also termed SeM) is a cell-wall-associated anti-phagocytic M-like protein of the equine pathogen Streptococcus equi subsp. equi, and binds fibrinogen (Fg) and IgG. FgBP binds Fg avidly through residues located at the extreme N terminus of the molecule, whereas the IgG-binding site is more centrally located between the A and B repeats. FgBP binds equine IgG4 and IgG7 subclasses through interaction with the CH2–CH3 interdomain region of IgG-Fc, and possesses overlapping Fc-binding sites with protein A and protein G. In this study, FgBP truncates containing defined internal deletions were used to identify a stretch of 14 aa (residues 335–348) critical for IgG binding. Protein chimeras consisting of the non-IgG-binding α-helical coiled-coil M5 protein fused to FgBP sequences were used to identify a minimal equine IgG-binding domain consisting of residues 329–360. Competition ELISA tests suggested that IgG does not compromise Fg binding and vice versa.

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“…The IgG-binding domain of Mrp does not have any significant degree of similarity to the IgG-binding domains of M proteins and protein H, as described by Pack et al [23] or to the IgA-binding domains of M proteins and M-like proteins described by others [9,13,24]. …”

Section: Discussionmentioning

confidence: 93%

Non-Immune Binding of Human IgG to M-Related Proteins Confers Resistance to Phagocytosis of Group A Streptococci in Blood

Courtney

2013

PLoS ONE

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The non-immune binding of immunoglobulins by bacteria is thought to contribute to the pathogenesis of infections. M-related proteins (Mrp) are group A streptococcal (GAS) receptors for immunoglobulins, but it is not known if this binding has any impact on virulence. To further investigate the binding of immunoglobulins to Mrp, we engineered mutants of an M type 4 strain of GAS by inactivating the genes for mrp, emm, enn, sof, and sfbX and tested these mutants in IgG-binding assays. Inactivation of mrp dramatically decreased the binding of human IgG, whereas inactivation of emm, enn, sof, and sfbx had only minor effects, indicating that Mrp is a major IgG-binding protein. Binding of human immunoglobulins to a purified, recombinant form of Mrp indicated that it selectively binds to the Fc domain of human IgG, but not IgA or IgM and that it preferentially bound subclasses IgG1>IgG4>IgG2>IgG3. Recombinant proteins encompassing different regions of Mrp were engineered and used to map its IgG-binding domain to its A-repeat region and a recombinant protein with 3 A-repeats was a better inhibitor of IgG binding than one with a single A-repeat. A GAS mutant expressing Mrp with an in-frame deletion of DNA encoding the A-repeats had a dramatically reduced ability to bind human IgG and to grow in human blood. Mrp exhibited host specificity in binding IgG; human IgG was the best inhibitor of the binding of IgG followed by pig, horse, monkey, and rabbit IgG. IgG from goat, mouse, rat, cow, donkey, chicken, and guinea pig were poor inhibitors of binding. These findings indicate that Mrp preferentially binds human IgG and that this binding contributes to the ability of GAS to resist phagocytosis and may be a factor in the restriction of GAS infections to the human host.

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Identification of an amino acid signature sequence predictive of protein G-inhibitable IgG3-binding activity in group-A streptococcal IgG-binding proteins

Cited by 13 publications

References 21 publications

Interaction between Complement Regulators andStreptococcus pyogenes: Binding of C4b-Binding Protein and Factor H/Factor H-Like Protein 1 to M18 Strains Involves Two Different Cell Surface Molecules

Interaction between Complement Regulators andStreptococcus pyogenes: Binding of C4b-Binding Protein and Factor H/Factor H-Like Protein 1 to M18 Strains Involves Two Different Cell Surface Molecules

Localization of the equine IgG-binding domain in the fibrinogen-binding protein (FgBP) of Streptococcus equi subsp. equi

Non-Immune Binding of Human IgG to M-Related Proteins Confers Resistance to Phagocytosis of Group A Streptococci in Blood

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