Publication Date:
2011-04-09
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268815/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268815/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Macheboeuf, Pauline -- Buffalo, Cosmo -- Fu, Chi-yu -- Zinkernagel, Annelies S -- Cole, Jason N -- Johnson, John E -- Nizet, Victor -- Ghosh, Partho -- R01 AI052453/AI/NIAID NIH HHS/ -- R01 AI052453-10/AI/NIAID NIH HHS/ -- R01 AI077780/AI/NIAID NIH HHS/ -- R01 AI077780-03/AI/NIAID NIH HHS/ -- R01 GM54076/GM/NIGMS NIH HHS/ -- R21 AI071167/AI/NIAID NIH HHS/ -- T32 GM007240/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Apr 7;472(7341):64-8. doi: 10.1038/nature09967.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21475196" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Bacterial Proteins/chemistry/*metabolism/ultrastructure
;
Binding Sites
;
Crystallography, X-Ray
;
Fibrinogen/*chemistry/metabolism/ultrastructure
;
Humans
;
Models, Molecular
;
Neutrophil Activation
;
Protein Binding
;
Protein Conformation
;
Shock, Septic/microbiology/physiopathology
;
Streptococcus pyogenes/chemistry/*pathogenicity
;
Virulence
;
Virulence Factors/chemistry/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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