Factor IX: Difference between revisions
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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 <ref>PMID:3511981</ref>. | 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 <ref>PMID:3511981</ref>. | ||
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 | 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 <ref>PMID:4528109</ref>. In the absence of metal ions the Gla domain is highly disordered and unstructured which indicated that the metal ions, stabilize the structure <ref>PMID:1538724</ref>. 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. | ||
To identify the exact locations of bound Mg2+ ions, crystal structures comparisons were made between Mg2+-free and Mg2+-bound conditions. In the Mg2+-free conditions, Mg-1, Mg-7, and Mg-8, were replaced by Ca2+ ions which induced an elongation of the bond between the ion and an oxygen atom from a distance of 2.11 to 2.34 Å. This small change in distance induces a [[rotation of 4 degrees of FIX]]. This suggests that the magnisuim ions induce a closed form conformation that contributes to the tight association of the Gla domain. This situation probably arises mainly from a difference in length between O–Mg–O and O–Ca–O bridges. | To identify the exact locations of bound Mg2+ ions, crystal structures comparisons were made between Mg2+-free and Mg2+-bound conditions. In the Mg2+-free conditions, Mg-1, Mg-7, and Mg-8, were replaced by Ca2+ ions which induced an elongation of the bond between the ion and an oxygen atom from a distance of 2.11 to 2.34 Å. This small change in distance induces a [[rotation of 4 degrees of FIX]]. This suggests that the magnisuim ions induce a closed form conformation that contributes to the tight association of the Gla domain. This situation probably arises mainly from a difference in length between O–Mg–O and O–Ca–O bridges. | ||
