Streptococcal M1 protein constructs a pathological host fibrinogen network

Macheboeuf, Pauline, Buffalo, Cosmo, Fu, Chi-yu, Zinkernagel, Annelies S., Cole, Jason N., Johnson, John E., Nizet, Victor and Ghosh, Partho (2011) Streptococcal M1 protein constructs a pathological host fibrinogen network. Nature, 472 7341: 64-68. doi:10.1038/nature09967

Author Macheboeuf, Pauline
Buffalo, Cosmo
Fu, Chi-yu
Zinkernagel, Annelies S.
Cole, Jason N.
Johnson, John E.
Nizet, Victor
Ghosh, Partho
Title Streptococcal M1 protein constructs a pathological host fibrinogen network
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2011-04-07
Sub-type Article (original research)
DOI 10.1038/nature09967
Open Access Status Not Open Access
Volume 472
Issue 7341
Start page 64
End page 68
Total pages 5
Place of publication London, United Kingdom
Publisher Nature
Language eng
Formatted 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.
Keyword Microbiology
Structural biology
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Additional 2 pages on methods

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 43 times in Thomson Reuters Web of Science Article | Citations
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