Streptococcal M1 protein constructs a pathological host fibrinogen network

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 (Fg) that, unlike M1 or Fg alone, leads to neutrophil activation. Here we provide a structural explanation for the pathological properties of the M1-Fg complex. A conformationally dynamic coiled-coil dimer of M1 was found to organize four Fg 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.