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[[Image:1lt9.jpg|left|200px]]


{{Structure
==Crystal Structure of Recombinant Human Fibrinogen Fragment D==
|PDB= 1lt9 |SIZE=350|CAPTION= <scene name='initialview01'>1lt9</scene>, resolution 2.80&Aring;
<StructureSection load='1lt9' size='340' side='right'caption='[[1lt9]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>
<table><tr><td colspan='2'>[[1lt9]] is a 6 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=1LT9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LT9 FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
|GENE=  
<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>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lt9 OCA], [https://pdbe.org/1lt9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lt9 RCSB], [https://www.ebi.ac.uk/pdbsum/1lt9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lt9 ProSAT]</span></td></tr>
|RELATEDENTRY=[[1fza|1FZA]], [[1fzb|1FZB]], [[1fzc|1FZC]], [[1fze|1FZE]], [[1fzf|1FZF]], [[1fzg|1FZG]], [[1ltj|1LTJ]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lt9 OCA], [http://www.ebi.ac.uk/pdbsum/1lt9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lt9 RCSB]</span>
== 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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lt/1lt9_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1lt9 ConSurf].
<div style="clear:both"></div>


'''Crystal Structure of Recombinant Human Fibrinogen Fragment D'''
==See Also==
 
*[[Fibrinogen|Fibrinogen]]
 
== References ==
==Overview==
<references/>
We report two crystal structures, each at a resolution of 2.8 A, of recombinant human fibrinogen fragment D (rfD) in the absence and presence of peptide ligands. The bound ligands, Gly-Pro-Arg-Pro-amide and Gly-His-Arg-Pro-amide, mimic the interactions of the thrombin exposed polymerization sites, "A" and "B", respectively. This report is the first to describe the structure of fragment D in the presence of both peptide ligands. The structures reveal that recombinant fibrinogen is nearly identical to the plasma protein but with minor changes, like the addition of a proximal fucose to the carbohydrate linked to residue betaGln364, and slightly different relative positions of the beta- and gamma-modules. Of major interest in our structures is that a previously identified calcium site in plasma fibrinogen is absent when Gly-His-Arg-Pro-amide is bound. The peptide-dependent loss of this calcium site may have significant biological implications that are further discussed. These structures provide a foundation for the detailed structural analysis of variant recombinant fibrinogens that were used to identify critical functional residues within fragment D.
__TOC__
 
</StructureSection>
==About this Structure==
1LT9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LT9 OCA].
 
==Reference==
2.8 A crystal structures of recombinant fibrinogen fragment D with and without two peptide ligands: GHRP binding to the "b" site disrupts its nearby calcium-binding site., Kostelansky MS, Betts L, Gorkun OV, Lord ST, Biochemistry. 2002 Oct 8;41(40):12124-32. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12356313 12356313]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Betts, L.]]
[[Category: Betts L]]
[[Category: Gorkun, O V.]]
[[Category: Gorkun OV]]
[[Category: Kostelansky, M S.]]
[[Category: Kostelansky MS]]
[[Category: Lord, S T.]]
[[Category: Lord ST]]
[[Category: blood coagulation]]
[[Category: fibrinogen]]
[[Category: fibrinogen fragment d]]
[[Category: recombinant fibrinogen]]
[[Category: recombinant fibrinogen fragment d]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:07:06 2008''

Latest revision as of 11:27, 10 April 2024

Crystal Structure of Recombinant Human Fibrinogen Fragment DCrystal Structure of Recombinant Human Fibrinogen Fragment D

Structural highlights

1lt9 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

See Also

References

  1. ↑ 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

1lt9, resolution 2.80Å

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