User:Manon Raiffort/Sandbox: Difference between revisions

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== Function ==

Von Willebrand factor has several functions in ~~diferent~~ phenomenon :

Von Willebrand factor has several functions in different phenomenon :

* '''Primary haemostasis''' : Afer a damaged of blood vessels, platelets will adhere to subendothelium which is a thrombogenic surface thanks to vWF. The platelet plug is formed thaks to the platelets aggregation. Domain A1 of vWF links to the receptor Gp-1b-IX-V, which is found on platelet.

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*''' Coagulation''' = Secondary Haemostasis : The goal of this step is to create a thrombus. Numerous coagulated factors are involved during this process. The plasma procoagulant co-enzyme Factor VIII plays a central role in the coagulation : catalyses activation of factor X and stabilizes the thrombus which stop the bleeding. vWF acts as a carrier for this factor. The factor VIII is bound to two domains : D'/D3. Without vWF the factor VIII will be cleaved by serin proteases.

* Interaction with '''[[Collagen]]''' : On the one hand the A1 and A3 domains of vWF link to the collagen of the subepithelium and on the other hand it binds to the platelets thanks to Gp Ib receptor.

* Interaction with '''[[Collagen]]''' : On the one hand the A1 and A3 domains of vWF link to the collagen of the subepithelium and on the other hand it binds to the platelets thanks to Gp Ib receptor. The collagen have some residues positively charged. However some residues of the A3 domain of the vWF are negatively charged. Some studies suggests that the interaction between collagen and the A3 domains is possible thanks to these charges<ref>Huizinga et el. (1997)Crystal structure of the A3 domain of human von Willebrand factor: implications for collagen binding, http://www.cell.com/structure/fulltext/S0969-2126(97)00266-9.</ref>.

* Interaction with receptor of '''platelet integrins αIIb/β3 ''' by the C1 domain which contains the RGD pattern : Arg-Gly-Asp

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Von Willebrand factor is directly or indirectly responsible of some diseases.

In the directly way, the von willebrand disease is caused by a mutation or by hereditary transmission. They are due to an anomaly qualitative or quantitative of the factor. There is 3 types of von Willebrand diseases : in the type I and II, the hereditary transmission is involved (there is 50% chance that the child got the defect gene). But in type III, the child receives the defect gene of the both parents. It is necessary to determine which type a patient has in order to give them the right treatment.

In the directly way, the von willebrand disease is caused by a mutation or by hereditary transmission. They are due to an anomaly qualitative or quantitative of the factor. There is 3 types of von Willebrand diseases<ref>Federation mondiale de l'Hémophilie, https://www.wfh.org/fr/page.aspx?pid=1134.</ref> : in the type I and II, the hereditary transmission is involved (there is 50% chance that the child got the defect gene). But in type III, the child receives the defect gene of the both parents. It is necessary to determine which type a patient has in order to give them the right treatment.

* '''Type I''' : It's a partial quantitative deficit. The factor works correctly but is present in insufficient quantity.

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== Structural highlights ==

===Generalities ===

Each monomer is composed of 11 domains : D’-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2

Each monomer is composed of 11 domains : D’-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2<ref>Purification of human von Willebrand factor–cleaving protease and its identification as a new member of the metalloproteinase family, http://www.bloodjournal.org/content/98/6/1662?sso-checked=true.</ref>.

* D'/D3 : Links to factor VIII

* A1 : Links to GPIb Receptor of platelet and collagen

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=== A3 domain ===

Phrase<ref>{{article|auteur1=Marc Jezegabel|titre=1967 Vive le Québec libre|périodique=[[Le Figaro]]|volume=1|jour=12|mois=mars|année=2007 |lire en ligne=http://www.lefigaro.fr/debats/2007/03/12/01005-20070312ARTFIG90125-_vive_le_quebec_libre.php}} {{citation|blablablablabla}}</ref>.

A3 domain is a domain of 20kDa between the residues 920 to 1111 of the von willebrand factor.

It has a dinucleotide-binding fold. This is a structure in which a central β sheet is encompassed by 7 α-helix (named α1 to α7) connected by loops. The β sheet is composed by 6 strands (named respectively β1 to β6) and are all parallel except the β3 which is on the sheet’s edge.

It has <scene name='75/750301/Secondary_structure/1'> a dinucleotide-binding fold </scene>. This is a structure in which a central β sheet is encompassed by <scene name='75/750301/Alpha_helix/1'>7 α-helix</scene> (named α1 to α7) connected by loops. The β sheet (yellow) is composed by 6 strands (named respectively β1 to β6) and are all parallel except the β3 which is on the sheet’s edge.

In this domain, two cysteine residues (923 and 1109) put the N-terminal and C-terminal region together by a disulfide bond.

The A3 domain is composed of negative charged and this allows the interaction with the collagen which has positive charged residues on it.

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

== References ==

*~~Kazuo Fujikawa et al.~~ (~~2001~~)~~. Purification of human von Willebrand factor–cleaving protease and its identification as a new member of the metalloproteinase family~~. Blood http://www.bloodjournal.org/content/98/6/~~1662~~.~~long~~?sso-checked=true ~~<references/>~~

*Eric G Huizinga1 et al. (1997) Crystal structure of the A3 domain of human von Willebrand factor: implications for collagen binding. Cell Press <references/>

* Hans Deckmyn and Karen Vanhoorelbeke, (2006) When collagen meets VWF. Blood [[http://www.bloodjournal.org/content/bloodjournal/108/12/3628.full.pdf?sso-checked=true]]

*Zaverio M. Ruggeri (2001). Structure of von Willebrand factor and its function in platelet adhesion and thrombus formation. ~~Elsevier <references/>~~

*Zaverio M. Ruggeri (2001) Structure of von Willebrand factor and its function in platelet adhesion and thrombus formation. Best Practice & Research Clinical Haematology

@@ Line 25: / Line 25: @@
 == Function ==
-Von Willebrand factor has several functions in diferent phenomenon :
+Von Willebrand factor has several functions in different phenomenon :
 * '''Primary haemostasis''' : Afer a damaged of blood vessels, platelets will adhere to subendothelium which is a thrombogenic surface thanks to vWF. The platelet plug is formed thaks to the platelets aggregation. Domain A1 of vWF links to the receptor Gp-1b-IX-V, which is found on platelet.
@@ Line 31: / Line 31: @@
 *''' Coagulation''' = Secondary Haemostasis : The goal of this step is to create a thrombus. Numerous coagulated factors are involved during this process. The plasma procoagulant co-enzyme Factor VIII plays a central role in the coagulation : catalyses activation of factor X and stabilizes the thrombus which stop the bleeding. vWF acts as a carrier for this factor. The factor VIII is bound to two domains : D'/D3. Without vWF the factor VIII will be cleaved by serin proteases.
-* Interaction with '''[[Collagen]]''' : On the one hand the A1 and A3 domains of vWF link to the collagen of the subepithelium and on the other hand it binds to the platelets thanks to Gp Ib receptor.
+* Interaction with '''[[Collagen]]''' : On the one hand the A1 and A3 domains of vWF link to the collagen of the subepithelium and on the other hand it binds to the platelets thanks to Gp Ib receptor. The collagen have some residues positively charged. However some residues of the A3 domain of the vWF are negatively charged. Some studies suggests that the interaction between collagen and the A3 domains is possible thanks to these charges<ref>Huizinga et el. (1997)Crystal structure of the A3 domain of human von Willebrand factor: implications for collagen binding, http://www.cell.com/structure/fulltext/S0969-2126(97)00266-9.</ref>.
 * Interaction with receptor of '''platelet integrins αIIb/β3 ''' by the C1 domain which contains the RGD pattern : Arg-Gly-Asp
@@ Line 40: / Line 40: @@
 Von Willebrand factor is directly or indirectly responsible of some diseases.
-In the directly way, the von willebrand disease is caused by a mutation or by hereditary transmission. They are due to an anomaly qualitative or quantitative of the factor. There is 3 types of von Willebrand diseases : in the type I and II, the hereditary transmission is involved (there is 50% chance that the child got the defect gene). But in type III, the child receives the defect gene of the both parents. It is necessary to determine which type a patient has in order to give them the right treatment.
+In the directly way, the von willebrand disease is caused by a mutation or by hereditary transmission. They are due to an anomaly qualitative or quantitative of the factor. There is 3 types of von Willebrand diseases<ref>Federation mondiale de l'Hémophilie, https://www.wfh.org/fr/page.aspx?pid=1134.</ref> : in the type I and II, the hereditary transmission is involved (there is 50% chance that the child got the defect gene). But in type III, the child receives the defect gene of the both parents. It is necessary to determine which type a patient has in order to give them the right treatment.
 * '''Type I''' : It's a partial quantitative deficit. The factor works correctly but is present in insufficient quantity.
@@ Line 57: / Line 57: @@
 == Structural highlights ==
 ===Generalities ===
-Each monomer is composed of 11 domains : D’-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2
+Each monomer is composed of 11 domains : D’-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2<ref>Purification of human von Willebrand factor–cleaving protease and its identification as a new member of the metalloproteinase family, http://www.bloodjournal.org/content/98/6/1662?sso-checked=true.</ref>.
 * D'/D3 : Links to factor VIII
 * A1 : Links to GPIb Receptor of platelet and collagen
@@ Line 65: / Line 65: @@
 === A3 domain ===
-Phrase<ref>{{article|auteur1=Marc Jezegabel|titre=1967 Vive le Québec libre|périodique=[[Le Figaro]]|volume=1|jour=12|mois=mars|année=2007 |lire en ligne=http://www.lefigaro.fr/debats/2007/03/12/01005-20070312ARTFIG90125-_vive_le_quebec_libre.php}} {{citation|blablablablabla}}</ref>.
 A3 domain is a domain of 20kDa between the residues 920 to 1111 of the von willebrand factor.
-It has a dinucleotide-binding fold. This is a structure in which a central β sheet is encompassed by 7 α-helix (named α1 to α7) connected by loops. The β sheet is composed by 6 strands (named respectively β1 to β6) and are all parallel except the β3 which is on the sheet’s edge.
+It has <scene name='75/750301/Secondary_structure/1'> a dinucleotide-binding fold </scene>. This is a structure in which a central β sheet is encompassed by <scene name='75/750301/Alpha_helix/1'>7 α-helix</scene>  (named α1 to α7)  connected by loops. The β sheet (yellow) is composed by 6 strands (named respectively β1 to β6) and are all parallel except the β3 which is on the sheet’s edge.
 In this domain, two cysteine residues (923 and 1109) put the N-terminal and C-terminal region together by a disulfide bond.
 The A3 domain is composed of negative charged and this allows the interaction with the collagen which has positive charged residues on it.
-This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
 == References ==
-*Kazuo Fujikawa et al. (2001). Purification of human von Willebrand factor–cleaving protease and its identification as a new member of the metalloproteinase family. Blood http://www.bloodjournal.org/content/98/6/1662.long?sso-checked=true <references/>
+<references />
-*Eric G Huizinga1 et al. (1997) Crystal structure of the A3 domain of human von Willebrand factor: implications for collagen binding. Cell Press <references/>
+* Hans Deckmyn and Karen Vanhoorelbeke, (2006) When collagen meets VWF. Blood [[http://www.bloodjournal.org/content/bloodjournal/108/12/3628.full.pdf?sso-checked=true]]
-*Zaverio M. Ruggeri (2001). Structure of von Willebrand factor and its function in platelet adhesion and thrombus formation. Elsevier <references/>
+*Zaverio M. Ruggeri (2001) Structure of von Willebrand factor and its function in platelet adhesion and thrombus formation. Best Practice & Research Clinical Haematology