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{{STRUCTURE_1sq0|  PDB=1sq0  |  SCENE=  }}
===Crystal Structure of the Complex of the Wild-type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom Resolution===
{{ABSTRACT_PUBMED_15039442}}


==Disease==
==Crystal Structure of the Complex of the Wild-type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom Resolution==
[[http://www.uniprot.org/uniprot/VWF_HUMAN VWF_HUMAN]] Defects in VWF are the cause of von Willebrand disease type 1 (VWD1) [MIM:[http://omim.org/entry/193400 193400]]. A common hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 1 is characterized by partial quantitative deficiency of circulating von Willebrand factor, that is otherwise structurally and functionally normal. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.<ref>PMID:10887119</ref><ref>PMID:11698279</ref> Defects in VWF are the cause of von Willebrand disease type 2 (VWD2) [MIM:[http://omim.org/entry/613554 613554]]. A hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 2 is characterized by qualitative deficiency and functional anomalies of von Willebrand factor. It is divided in different subtypes including 2A, 2B, 2M and 2N (Normandy variant). The mutant VWF protein in types 2A, 2B and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind factor VIII. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.  Defects in VWF are the cause of von Willebrand disease type 3 (VWD3) [MIM:[http://omim.org/entry/277480 277480]]. A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses. [[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[http://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref>  Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[http://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref><ref>PMID:7690774</ref><ref>PMID:7819107</ref><ref>PMID:7873390</ref><ref>PMID:9639514</ref><ref>PMID:10089893</ref>  Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[http://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref>  Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[http://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref><ref>PMID:2052556</ref><ref>PMID:8486780</ref><ref>PMID:8384898</ref>
<StructureSection load='1sq0' size='340' side='right'caption='[[1sq0]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 
== Structural highlights ==
==Function==
<table><tr><td colspan='2'>[[1sq0]] is a 2 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=1SQ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SQ0 FirstGlance]. <br>
[[http://www.uniprot.org/uniprot/VWF_HUMAN VWF_HUMAN]] Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma. [[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</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=1sq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sq0 OCA], [https://pdbe.org/1sq0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sq0 RCSB], [https://www.ebi.ac.uk/pdbsum/1sq0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sq0 ProSAT]</span></td></tr>
==About this Structure==
</table>
[[1sq0]] is a 2 chain structure with sequence 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=1SQ0 OCA].  
== Disease ==
[https://www.uniprot.org/uniprot/VWF_HUMAN VWF_HUMAN] Defects in VWF are the cause of von Willebrand disease type 1 (VWD1) [MIM:[https://omim.org/entry/193400 193400]. A common hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 1 is characterized by partial quantitative deficiency of circulating von Willebrand factor, that is otherwise structurally and functionally normal. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.<ref>PMID:10887119</ref> <ref>PMID:11698279</ref>   Defects in VWF are the cause of von Willebrand disease type 2 (VWD2) [MIM:[https://omim.org/entry/613554 613554]. A hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 2 is characterized by qualitative deficiency and functional anomalies of von Willebrand factor. It is divided in different subtypes including 2A, 2B, 2M and 2N (Normandy variant). The mutant VWF protein in types 2A, 2B and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind factor VIII. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.  Defects in VWF are the cause of von Willebrand disease type 3 (VWD3) [MIM:[https://omim.org/entry/277480 277480]. A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses.
== Function ==
[https://www.uniprot.org/uniprot/VWF_HUMAN VWF_HUMAN] Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma.
== 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/sq/1sq0_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=1sq0 ConSurf].
<div style="clear:both"></div>


==See Also==
==See Also==
*[[Platelet-receptor glycoprotein Ib alpha|Platelet-receptor glycoprotein Ib alpha]]
*[[Platelet glycoprotein|Platelet glycoprotein]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:015039442</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Dumas, J J.]]
[[Category: Large Structures]]
[[Category: Kumar, R.]]
[[Category: Dumas JJ]]
[[Category: McDonagh, T.]]
[[Category: Kumar R]]
[[Category: Mosyak, L.]]
[[Category: McDonagh T]]
[[Category: Somers, W S.]]
[[Category: Mosyak L]]
[[Category: Stahl, M L.]]
[[Category: Somers WS]]
[[Category: Sullivan, F.]]
[[Category: Stahl ML]]
[[Category: Blood clotting]]
[[Category: Sullivan F]]

Latest revision as of 11:34, 1 May 2024

Crystal Structure of the Complex of the Wild-type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom ResolutionCrystal Structure of the Complex of the Wild-type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom Resolution

Structural highlights

1sq0 is a 2 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 2.6Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

VWF_HUMAN Defects in VWF are the cause of von Willebrand disease type 1 (VWD1) [MIM:193400. A common hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 1 is characterized by partial quantitative deficiency of circulating von Willebrand factor, that is otherwise structurally and functionally normal. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.[1] [2] Defects in VWF are the cause of von Willebrand disease type 2 (VWD2) [MIM:613554. A hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 2 is characterized by qualitative deficiency and functional anomalies of von Willebrand factor. It is divided in different subtypes including 2A, 2B, 2M and 2N (Normandy variant). The mutant VWF protein in types 2A, 2B and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind factor VIII. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma. Defects in VWF are the cause of von Willebrand disease type 3 (VWD3) [MIM:277480. A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses.

Function

VWF_HUMAN Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma.

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. ↑ Allen S, Abuzenadah AM, Hinks J, Blagg JL, Gursel T, Ingerslev J, Goodeve AC, Peake IR, Daly ME. A novel von Willebrand disease-causing mutation (Arg273Trp) in the von Willebrand factor propeptide that results in defective multimerization and secretion. Blood. 2000 Jul 15;96(2):560-8. PMID:10887119
  2. ↑ Bodo I, Katsumi A, Tuley EA, Eikenboom JC, Dong Z, Sadler JE. Type 1 von Willebrand disease mutation Cys1149Arg causes intracellular retention and degradation of heterodimers: a possible general mechanism for dominant mutations of oligomeric proteins. Blood. 2001 Nov 15;98(10):2973-9. PMID:11698279

1sq0, resolution 2.60Å

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