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| - | {{STRUCTURE_2xnx| PDB=2xnx | SCENE= }}
| + | ==BC1 FRAGMENT OF STREPTOCOCCAL M1 PROTEIN IN COMPLEX WITH HUMAN FIBRINOGEN== |
| - | ===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=''> |
| - | {{ABSTRACT_PUBMED_21475196}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2xnx]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XNX FirstGlance]. <br> |
| | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vdo|2vdo]], [[1rf1|1rf1]], [[1fzb|1fzb]], [[1fid|1fid]], [[2vdp|2vdp]], [[1lt9|1lt9]], [[1fzc|1fzc]], [[1n8e|1n8e]], [[2vdr|2vdr]], [[2vdq|2vdq]], [[1re4|1re4]], [[1n86|1n86]], [[1dug|1dug]], [[1re3|1re3]], [[1fza|1fza]], [[1fzd|1fzd]], [[1ltj|1ltj]], [[1fph|1fph]], [[1fzg|1fzg]], [[2ffd|2ffd]], [[2fib|2fib]], [[1fzf|1fzf]], [[1fze|1fze]], [[1rf0|1rf0]], [[1fic|1fic]], [[2y7l|2y7l]], [[1fib|1fib]], [[3fib|3fib]], [[1bbr|1bbr]], [[2vr3|2vr3]], [[2xny|2xny]]</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xnx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xnx RCSB], [http://www.ebi.ac.uk/pdbsum/2xnx PDBsum]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [[http://www.uniprot.org/uniprot/FIBA_HUMAN FIBA_HUMAN]] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:[http://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:[http://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> [[http://www.uniprot.org/uniprot/FIBG_HUMAN FIBG_HUMAN]] Defects in FGG are a cause of congenital afibrinogenemia (CAFBN) [MIM:[http://omim.org/entry/202400 202400]]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding. [[http://www.uniprot.org/uniprot/FIBB_HUMAN FIBB_HUMAN]] Defects in FGB are a cause of congenital afibrinogenemia (CAFBN) [MIM:[http://omim.org/entry/202400 202400]]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding. |
| | + | == Function == |
| | + | [[http://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. [[http://www.uniprot.org/uniprot/FIBG_HUMAN FIBG_HUMAN]] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. [[http://www.uniprot.org/uniprot/FIBB_HUMAN FIBB_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. |
| | | | |
| - | ==Disease==
| + | 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> |
| - | [[http://www.uniprot.org/uniprot/FIBA_HUMAN FIBA_HUMAN]] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:[http://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:[http://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> [[http://www.uniprot.org/uniprot/FIBG_HUMAN FIBG_HUMAN]] Defects in FGG are a cause of congenital afibrinogenemia (CAFBN) [MIM:[http://omim.org/entry/202400 202400]]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding. [[http://www.uniprot.org/uniprot/FIBB_HUMAN FIBB_HUMAN]] Defects in FGB are a cause of congenital afibrinogenemia (CAFBN) [MIM:[http://omim.org/entry/202400 202400]]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding.
| + | |
| | | | |
| - | ==Function==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[http://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. [[http://www.uniprot.org/uniprot/FIBG_HUMAN FIBG_HUMAN]] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. [[http://www.uniprot.org/uniprot/FIBB_HUMAN FIBB_HUMAN]] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.
| + | </div> |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | [[2xnx]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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].
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Fibrinogen|Fibrinogen]] | | *[[Fibrinogen|Fibrinogen]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:021475196</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Streptococcus pyogenes]] | | [[Category: Streptococcus pyogenes]] |
| - | [[Category: Fu, C Y.]] | + | [[Category: Fu, C Y]] |
| - | [[Category: Ghosh, P.]] | + | [[Category: Ghosh, P]] |
| - | [[Category: Johnson, J E.]] | + | [[Category: Johnson, J E]] |
| - | [[Category: Macheboeuf, P.]] | + | [[Category: Macheboeuf, P]] |
| - | [[Category: Nizet, V.]] | + | [[Category: Nizet, V]] |
| - | [[Category: Zinkernagel, A S.]] | + | [[Category: Zinkernagel, A S]] |
| | [[Category: Cell adhesion]] | | [[Category: Cell adhesion]] |
| | [[Category: Streptococcal toxic shock syndrome]] | | [[Category: Streptococcal toxic shock syndrome]] |
| | [[Category: Virulence factor]] | | [[Category: Virulence factor]] |
| Structural highlights
2xnx is a 14 chain structure with sequence from Homo sapiens and Streptococcus pyogenes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 2vdo, 1rf1, 1fzb, 1fid, 2vdp, 1lt9, 1fzc, 1n8e, 2vdr, 2vdq, 1re4, 1n86, 1dug, 1re3, 1fza, 1fzd, 1ltj, 1fph, 1fzg, 2ffd, 2fib, 1fzf, 1fze, 1rf0, 1fic, 2y7l, 1fib, 3fib, 1bbr, 2vr3, 2xny |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[FIBA_HUMAN] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM: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: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.[1] [FIBG_HUMAN] Defects in FGG are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding. [FIBB_HUMAN] Defects in FGB are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding.
Function
[FIBA_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. [FIBG_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. [FIBB_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Nat Genet. 1993 Mar;3(3):252-5. PMID:8097946 doi:http://dx.doi.org/10.1038/ng0393-252
- ↑ Macheboeuf P, Buffalo C, Fu CY, Zinkernagel AS, Cole JN, Johnson JE, Nizet V, Ghosh P. Streptococcal M1 protein constructs a pathological host fibrinogen network. Nature. 2011 Apr 7;472(7341):64-8. PMID:21475196 doi:10.1038/nature09967
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