Sandbox Reserved 1482: Difference between revisions

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== '''Coagulation Factor VIII (3cdz)''' ==
== '''Coagulation Factor VIII (3cdz)''' ==
<StructureSection load='3cdz' size='340' side='right' caption='The human coagulation factor VIII' scene=''>
<StructureSection load='3cdz' size='340' side='right' caption='The human coagulation factor VIII' scene=''>
'''The human Factor VIII''', also known as anti-hemophilic factor (AHF), is an essential blood-clotting protein <ref>Wikipedia, Factor VIII (https://en.wikipedia.org/wiki/Factor_VIII)</ref>. It consists of 2332 residues <sup>[9]</sup>, whose gene is located on the X chromosome <sup>[4,8]</sup>.  
'''The human Factor VIII''', also known as anti-hemophilic factor (AHF), is an essential blood-clotting protein <ref name="wikipedia">Wikipedia, Factor VIII (https://en.wikipedia.org/wiki/Factor_VIII)</ref>. It consists of 2332 residues <sup>[9]</sup>, whose gene is located on the X chromosome <sup>[4,8]</sup>.  


Factor VIII is produced inside the liver (by the sinusoidal cells) and outside (by the endothelial cells) and acts in the intrinsic pathway of blood coagulation <ref>Wikipedia, Factor VIII (https://en.wikipedia.org/wiki/Factor_VIII)</ref> <sup>[8]</sup>. It is actually the lack or the deficiency of the factor VIII (which is a plasma glycoprotein) that causes a bleeding disorder: hemophilia A <sup>[9]</sup>.
Factor VIII is produced inside the liver (by the sinusoidal cells) and outside (by the endothelial cells) and acts in the intrinsic pathway of blood coagulation <ref name="wikipedia" /> <sup>[8]</sup>. It is actually the lack or the deficiency of the factor VIII (which is a plasma glycoprotein) that causes a bleeding disorder: hemophilia A <sup>[9]</sup>.


Factor VIII is much studied in order to find a cure for hemophilia A (also written as HEMA), for instance by designing mimicking factors <sup>[12]</sup>.  
Factor VIII is much studied in order to find a cure for hemophilia A (also written as HEMA), for instance by designing mimicking factors <sup>[12]</sup>.  
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The three A domains are homologous to the A domains of the copper-binding protein ceruloplasmin <sup>[8,14]</sup>. Together, they form a triangular heterotrimer where the A<sub>1</sub> and A<sub>3</sub> domains interact with the C<sub>2</sub> and C<sub>1</sub> domains, respectively <sup>[9]</sup>.
The three A domains are homologous to the A domains of the copper-binding protein ceruloplasmin <sup>[8,14]</sup>. Together, they form a triangular heterotrimer where the A<sub>1</sub> and A<sub>3</sub> domains interact with the C<sub>2</sub> and C<sub>1</sub> domains, respectively <sup>[9]</sup>.


The C domains belong to the phospholipid-binding discoidin domain family <ref>Wikipedia, Factor VIII (https://en.wikipedia.org/wiki/Factor_VIII)</ref> <sup>[8]</sup>. They are adjacent at the base of the triangular heterotrimer. Moreover, C<sub>1</sub> and C<sub>2</sub> domains are structurally homologous and they have the ability to bind the membrane. Indeed, both C domain protrude three β-hairpin loops with hydrophobic and basic residues in the same direction. Thanks to these loops the factor VIII might interact with the phospholipid bilayer. <sup>[9]</sup>
The C domains belong to the phospholipid-binding discoidin domain family <ref name="wikipedia" /> <sup>[8]</sup>. They are adjacent at the base of the triangular heterotrimer. Moreover, C<sub>1</sub> and C<sub>2</sub> domains are structurally homologous and they have the ability to bind the membrane. Indeed, both C domain protrude three β-hairpin loops with hydrophobic and basic residues in the same direction. Thanks to these loops the factor VIII might interact with the phospholipid bilayer. <sup>[9]</sup>




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Both chains are no covalently associated through to a calcium ion to form the active heterodimers <sup>[3,9]</sup>. This complex is the pro-coagulant factor VIIIa <ref>Wikipedia, Factor VIII (https://en.wikipedia.org/wiki/Factor_VIII)</ref> <sup>[8]</sup>.  
Both chains are no covalently associated through to a calcium ion to form the active heterodimers <sup>[3,9]</sup>. This complex is the pro-coagulant factor VIIIa <ref name="wikipedia" /> <sup>[8]</sup>.  
Such an association is essentialfor the functioning of the factor VIII <sup>[3]</sup>.  
Such an association is essentialfor the functioning of the factor VIII <sup>[3]</sup>.