Amino acid sequence and physicochemical similarities between streptococcal M protein and mammalian tropomyosin.

Hosein, Barbara; McCarty, Maclyn; Fischetti, Vincent A.

doi:10.1073/pnas.76.8.3765

Cited by 28 publications

(27 citation statements)

References 38 publications

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“…Thus, the binding was probably mediated by interactions of negatively charged sites on the bacterial surface with the positively charged collagenous ligand binding domain of the receptor. Experiments using S. pyogenes mutants showed that the binding was independent of the hyaluronic acid capsule and the M protein, two major surface virulence determinants specific for S. pyogenes (16,(20)(21)(22)(23)(24)(25). LTA, a polyanionic surface component found on most Gram-positive bacteria, was shown by competition assays to be a scavenger receptor ligand.…”

Section: Discussionmentioning

confidence: 99%

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The type I macrophage scavenger receptor binds togram-positive bacteria and recognizes lipoteichoic acid.

Dunne

Resnick

Greenberg

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

327

226

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Section: Discussionmentioning

confidence: 99%

“…To determine which cell surface component(s) on S. pyogenes might be responsible for scavenger receptor binding, we used mutant strains of S. pyogenes to assess the role in receptor binding of two wellcharacterized virulence determinants, M protein and the hyaluronic acid capsule (16,(20)(21)(22)(23)(24)(25). Fig.…”

Section: Methodsmentioning

confidence: 99%

The type I macrophage scavenger receptor binds togram-positive bacteria and recognizes lipoteichoic acid.

Dunne

Resnick

Greenberg

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

327

226

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“…M protein sequences are antigenically variable but have in common a strong propensity to form α-helical coiled coils (4). Paradoxically, these sequences are also replete with residues that destabilize coiled coils (5,6).…”

mentioning

confidence: 99%

Coiled-coil destabilizing residues in the group A Streptococcus M1 protein are required for functional interaction

Stewart

Buffalo

Valderrama

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The sequences of M proteins, the major surface-associated virulence factors of the widespread bacterial pathogen group A Streptococcus, are antigenically variable but have in common a strong propensity to form coiled coils. Paradoxically, these sequences are also replete with coiled-coil destabilizing residues. These features are evident in the irregular coiled-coil structure and thermal instability of M proteins. We present an explanation for this paradox through studies of the B repeats of the medically important M1 protein. The B repeats are required for interaction of M1 with fibrinogen (Fg) and consequent proinflammatory activation. The B repeats sample multiple conformations, including intrinsically disordered, dissociated, as well as two alternate coiled-coil conformations: a Fg-nonbinding register 1 and a Fg-binding register 2. Stabilization of M1 in the Fg-nonbinding register 1 resulted in attenuation of Fg binding as expected, but counterintuitively, so did stabilization in the Fg-binding register 2. Strikingly, these register-stabilized M1 proteins gained the ability to bind Fg when they were destabilized by a chaotrope. These results indicate that M1 stability is antithetical to Fg interaction and that M1 conformational dynamics, as specified by destabilizing residues, are essential for interaction. A "capture-and-collapse" model of association accounts for these observations, in which M1 captures Fg through a dynamic conformation and then collapses into a register 2-coiled coil as a result of stabilization provided by binding energy. Our results support the general conclusion that destabilizing residues are evolutionarily conserved in M proteins to enable functional interactions necessary for pathogenesis.M proteins are the major surface-associated virulence factors of group A Streptococcus (GAS; Streptococcus pyogenes) and play a significant role in the diverse diseases caused by this widespread bacterial pathogen (1-3). M protein sequences are antigenically variable but have in common a strong propensity to form α-helical coiled coils (4). Paradoxically, these sequences are also replete with residues that destabilize coiled coils (5, 6). These destabilizing residues occur at the central a and d positions of the coiled-coil [abcdefg] n heptad repeat (Fig. 1). For dimeric α-helical coiled coils, as is the case for M proteins (7-9), the a and d positions are preferentially occupied by Val and Leu, respectively (10, 11). These small, hydrophobic residues typically engage in "knobs-into-hole" packing and form the hydrophobic core of the coiled-coil dimer. In contrast, the a and d positions of M proteins are often occupied by coiled-coil destabilizing residues (e.g., charged residues or alanines), and the heptad pattern sometimes contains short insertions or deletions (Fig. 1B) (5, 9). These sorts of destabilizing residues and heptad disruptions result in a highly irregular coiled-coil structure in M1 protein (9). The high proportion of coiled-coil destabilizing residues is also consistent with M protei...

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“…One is that more than 100 different M serotypes have been identified and a number of clinical isolates have been M nontypeable (19,35). The other is that some M proteins share structural homology with cardiac proteins such as myosin and tropomyosin (10,17). The M19 protein possesses both a protective epitope and an autoimmune epitope in the amino terminus (2).…”

mentioning

confidence: 99%

Systemic and Mucosal Immunizations with Fibronectin-Binding Protein FBP54 Induce Protective Immune Responses againstStreptococcus pyogenesChallenge in Mice

et al. 2001

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The purpose of this study was to examine the suitability of fibronectin-binding protein FBP54 as a putative vaccine for Streptococcus pyogenes infections. When the distribution of the fbp54 gene among the clinical isolates representing various M serotypes was tested by PCR and Southern blot assays, it was found that all of the strains possess this gene. Furthermore, a significant increase in immunoglobulin G (IgG) antibody titers against FBP54 was observed in sera from patients with S. pyogenes infections compared with those from healthy volunteers (P < 0.005). Mice were immunized with FBP54 subcutaneously, orally, or nasally. An enzyme-linked immunosorbent assay revealed that antigen-specific IgG antibodies were induced in the sera of immunized mice, while high salivary levels of IgA antibodies were detected after oral and nasal immunizations. Mice subcutaneously or orally immunized with FBP54 survived significantly longer following the challenge with S. pyogenes than did nonimmunized mice (P < 0.001). These results indicate that FBP54 is a promising vaccine for the prevention of S. pyogenes infections.

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Amino acid sequence and physicochemical similarities between streptococcal M protein and mammalian tropomyosin.

Cited by 28 publications

References 38 publications

The type I macrophage scavenger receptor binds togram-positive bacteria and recognizes lipoteichoic acid.

The type I macrophage scavenger receptor binds togram-positive bacteria and recognizes lipoteichoic acid.

Coiled-coil destabilizing residues in the group A Streptococcus M1 protein are required for functional interaction

Systemic and Mucosal Immunizations with Fibronectin-Binding Protein FBP54 Induce Protective Immune Responses againstStreptococcus pyogenesChallenge in Mice

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