2xnx: Difference between revisions
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The entry | ==BC1 fragment of streptococcal M1 protein in complex with human fibrinogen== | ||
<StructureSection load='2xnx' size='340' side='right'caption='[[2xnx]], [[Resolution|resolution]] 3.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2xnx]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XNX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xnx OCA], [https://pdbe.org/2xnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xnx RCSB], [https://www.ebi.ac.uk/pdbsum/2xnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xnx ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/FIBA_HUMAN FIBA_HUMAN] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:[https://omim.org/entry/202400 202400]. This is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=The majority of cases of afibrinogenemia are due to truncating mutations. Variations in position Arg-35 (the site of cleavage of fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias. Defects in FGA are a cause of amyloidosis type 8 (AMYL8) [MIM:[https://omim.org/entry/105200 105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.<ref>PMID:8097946</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FIBA_HUMAN FIBA_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
Streptococcal M1 protein constructs a pathological host fibrinogen network.,Macheboeuf P, Buffalo C, Fu CY, Zinkernagel AS, Cole JN, Johnson JE, Nizet V, Ghosh P Nature. 2011 Apr 7;472(7341):64-8. PMID:21475196<ref>PMID:21475196</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2xnx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Fibrinogen|Fibrinogen]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Streptococcus pyogenes]] | |||
[[Category: Ghosh P]] | |||
[[Category: Johnson JE]] | |||
[[Category: Macheboeuf P]] | |||
[[Category: Nizet V]] | |||
[[Category: Y Fu C]] | |||
[[Category: Zinkernagel AS]] | |||