Streptococcal M1 protein constructs a pathological host fibrinogen network

Article

关键词: HEPARIN-BINDING PROTEIN;    GROUP-A STREPTOCOCCI;    OLIGOMERIZATION STATE;    CRYSTAL-STRUCTURE;    SURFACE-PROTEINS;    COILED COILS;    FRAGMENT-D;    CRYSTALLOGRAPHY;    PHAGOCYTOSIS;    STABILITY;   

DOI  :  10.1038/nature09967

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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