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Streptococcal M1 protein constructs a pathological host fibrinogen network.

ABSTRACT: M1 protein, a major virulence factor of the leading invasive strain of group A Streptococcus, is sufficient to induce toxic-shock-like vascular leakage and tissue injury. These events are triggered by the formation of a complex between M1 and fibrinogen that, unlike M1 or fibrinogen alone, leads to neutrophil activation. Here we provide a structural explanation for the pathological properties of the complex formed between streptococcal M1 and human fibrinogen. A conformationally dynamic coiled-coil dimer of M1 was found to organize four fibrinogen molecules into a specific cross-like pattern. This pattern supported the construction of a supramolecular network that was required for neutrophil activation but was distinct from a fibrin clot. Disruption of this network into other supramolecular assemblies was not tolerated. These results have bearing on the pathophysiology of streptococcal toxic shock.

SUBMITTER: Macheboeuf P

PROVIDER: S-EPMC3268815 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Streptococcal M1 protein constructs a pathological host fibrinogen network.

Macheboeuf Pauline P Buffalo Cosmo C Fu Chi-yu CY Zinkernagel Annelies S AS Cole Jason N JN Johnson John E JE Nizet Victor V Ghosh Partho P

Nature 20110401 7341

M1 protein, a major virulence factor of the leading invasive strain of group A Streptococcus, is sufficient to induce toxic-shock-like vascular leakage and tissue injury. These events are triggered by the formation of a complex between M1 and fibrinogen that, unlike M1 or fibrinogen alone, leads to neutrophil activation. Here we provide a structural explanation for the pathological properties of the complex formed between streptococcal M1 and human fibrinogen. A conformationally dynamic coiled-c ...[more]

PMID: 21475196

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