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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1fzg]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FZG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FZG FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1fzg]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FZG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FZG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=1fzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fzg OCA], [https://pdbe.org/1fzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fzg RCSB], [https://www.ebi.ac.uk/pdbsum/1fzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fzg ProSAT]</span></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=1fzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fzg OCA], [https://pdbe.org/1fzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fzg RCSB], [https://www.ebi.ac.uk/pdbsum/1fzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fzg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == 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> [[https://www.uniprot.org/uniprot/FIBG_HUMAN FIBG_HUMAN]] Defects in FGG are a cause of congenital afibrinogenemia (CAFBN) [MIM:[https://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. [[https://www.uniprot.org/uniprot/FIBB_HUMAN FIBB_HUMAN]] Defects in FGB are a cause of congenital afibrinogenemia (CAFBN) [MIM:[https://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.
| + | [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 == | | == 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. [[https://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. [[https://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.
| + | [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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Doolittle, R F]] | + | [[Category: Doolittle RF]] |
| - | [[Category: Everse, S J]] | + | [[Category: Everse SJ]] |
| - | [[Category: Spraggon, G]] | + | [[Category: Spraggon G]] |
| - | [[Category: Veerapandian, L]] | + | [[Category: Veerapandian L]] |
| - | [[Category: Blood coagulation]]
| + | |
| - | [[Category: Fibrin]]
| + | |
| - | [[Category: Fibrinogen]]
| + | |
| - | [[Category: Plasma]]
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| - | [[Category: Platelet]]
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| Structural highlights
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]
Function
FIBA_HUMAN Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The structure of fragment double-D from human fibrin has been solved in the presence and absence of the peptide ligands that simulate the two knobs exposed by the removal of fibrinopeptides A and B, respectively. All told, six crystal structures have been determined, three of which are reported here for the first time: namely, fragments D and double-D with the peptide GHRPam alone and double-D in the absence of any peptide ligand. Comparison of the structures has revealed a series of conformational changes that are brought about by the various knob-hole interactions. Of greatest interest is a moveable "flap" of two negatively charged amino acids (Glubeta397 and Aspbeta398) whose side chains are pinned back to the coiled coil with a calcium atom bridge until GHRPam occupies the beta-chain pocket. Additionally, in the absence of the peptide ligand GPRPam, GHRPam binds to the gamma-chain pocket, a new calcium-binding site being formed concomitantly.
Conformational changes in fragments D and double-D from human fibrin(ogen) upon binding the peptide ligand Gly-His-Arg-Pro-amide.,Everse SJ, Spraggon G, Veerapandian L, Doolittle RF Biochemistry. 1999 Mar 9;38(10):2941-6. PMID:10074346[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
- ↑ Everse SJ, Spraggon G, Veerapandian L, Doolittle RF. Conformational changes in fragments D and double-D from human fibrin(ogen) upon binding the peptide ligand Gly-His-Arg-Pro-amide. Biochemistry. 1999 Mar 9;38(10):2941-6. PMID:10074346 doi:http://dx.doi.org/10.1021/bi982626w
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