Factor IX: Difference between revisions
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== γ-Carboxyglutamic Acid (Gla) Domain == | == γ-Carboxyglutamic Acid (Gla) Domain == | ||
{{STRUCTURE_1j35| PDB=1j35 | SCENE= }} | {{STRUCTURE_1j35| PDB=1j35 | SCENE= }} | ||
The Gla domain is situated at the N-terminus of coagulation factor IX, and is evolutionary conserved in other | The Gla domain is situated at the N-terminus of coagulation factor IX, and is evolutionary conserved in other vitamin K dependent proteins such as factor VII, X, and prothrombin. A <scene name='Factor_IX/Gladomain_glamgca/2'>Gla domain</scene> is made up of 10-13 of γ-carboxyglutamic acid residues and requires both <scene name='Factor_IX/Gladomain_1/6'>Ca2+ and Mg2+ </scene> ions for membrane association and stabilization of its active three dimensional conformation (2-4). | ||
vitamin K dependent proteins such as factor VII, X, and prothrombin. A <scene name='Factor_IX/Gladomain_glamgca/2'>Gla domain</scene> is made up of 10-13 of γ-carboxyglutamic acid residues and requires | |||
both <scene name='Factor_IX/Gladomain_1/6'>Ca2+ and Mg2+ </scene> ions for membrane | |||
association and stabilization of its active three dimensional conformation (2-4). | |||
In the presence of [[calcium ions the Gla domain]] (Calcium ions 5 and 6 and Gla residues 17 and 21) interacts with serine head group of phosphatidylserine located on the phospholipid membrane (2). In the absence of metal ions the Gla domain is highly disordered and unstructured which indicated that the metal ions, stabilize the structure (4-6). Three Mg2+ ions, (Mg-1, Mg-7, and Mg-8) are located on the surface of FIX and correspond to FX, three Ca2+ ions (Ca-1, Ca-7, and Ca-8). Each Mg2+ ion has a <scene name='Factor_IX/Gladomain_1/7'>bipyramidal coordination</scene> with a water molecule (Mg–O in FIX is 2.12 Å, whereas the Ca–O distances in FX is 2.41 Å) and a pair of Gla residues. | In the presence of [[calcium ions the Gla domain]] (Calcium ions 5 and 6 and Gla residues 17 and 21) interacts with serine head group of phosphatidylserine located on the phospholipid membrane (2). In the absence of metal ions the Gla domain is highly disordered and unstructured which indicated that the metal ions, stabilize the structure (4-6). Three Mg2+ ions, (Mg-1, Mg-7, and Mg-8) are located on the surface of FIX and correspond to FX, three Ca2+ ions (Ca-1, Ca-7, and Ca-8). Each Mg2+ ion has a <scene name='Factor_IX/Gladomain_1/7'>bipyramidal coordination</scene> with a water molecule (Mg–O in FIX is 2.12 Å, whereas the Ca–O distances in FX is 2.41 Å) and a pair of Gla residues. | ||
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This structure emphasizes the possible role of magnesium in Gla domain binding to membrane surfaces. However upon examination of the calcium bound Factor IX-(1-46) complex revealed that the calcium coordination within this FIX Gla domain structure differes from other vitamin K-dependent proteins (prothrombin (7), Factor VII (10), and Factor X (11)). This deviation may be explained by the interaction of the snake venom FIX-bp interaction (this reference). | This structure emphasizes the possible role of magnesium in Gla domain binding to membrane surfaces. However upon examination of the calcium bound Factor IX-(1-46) complex revealed that the calcium coordination within this FIX Gla domain structure differes from other vitamin K-dependent proteins (prothrombin (7), Factor VII (10), and Factor X (11)). This deviation may be explained by the interaction of the snake venom FIX-bp interaction (this reference). | ||
{{STRUCTURE_1nl0| PDB=1nl0 | SCENE= }} | {{STRUCTURE_1nl0| PDB=1nl0 | SCENE= }} | ||
To further probe into the structure of FIX Gla domain, [[conformation-specific anti-Factor IX antibodies]] were utilized. Using an | To further probe into the structure of FIX Gla domain, [[conformation-specific anti-Factor IX antibodies]] were utilized. Using an | ||
<scene name='Factor_IX/Antifactor/1'>anti-Factor IX antibody</scene>, 10C12, which is then reformatted into a F(ab')2 form (two Fab fragments connected by a leucine zipper). This antibody is a calcium specific antibody for factor IX and provides information on the inhibition of membrane binding. by this conformation-specific antibody. The antibody interacts with the loop (Leu-6, Phe-9, and Val-10) of the -carboxyglutamic acids residues bound to calcium ions in the Gla domain. | <scene name='Factor_IX/Antifactor/1'>anti-Factor IX antibody</scene>, 10C12, which is then reformatted into a F(ab')2 form (two Fab fragments connected by a leucine zipper). This antibody is a calcium specific antibody for factor IX and provides information on the inhibition of membrane binding. by this conformation-specific antibody. The antibody interacts with the loop (Leu-6, Phe-9, and Val-10) of the -carboxyglutamic acids residues bound to calcium ions in the Gla domain. | ||