Factor IX: Difference between revisions

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The Gla domain perhaps also interacts with factor VIIIa via Mg2+-binding sites. Membrane bound FIXa forms an arched structure which is seen in the spatial relationship among the Gla, epidermal growth factor, and serine protease domains. This arched allows for the formation of a concave surface on the right side of FIXa and acts as a binding site for factor VIIIa. The Mg-8 ion points toward this concave surface making it ideal in the interaction between FIXa and GVIIIa. Similarly, [[Mg-8 may contribute to the binding to factors VIIa and X]].

Bovine Factor IX-(1-46) bound to a snake venom protein (Factor IX-bp), is crystallized in the presence of calcium and magnesium ions and in the presence of calcium alone.

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).

To further probe into the structure of FIX Gla domain, conformation-specific anti-Factor IX antibodies were utilized. Using an anti-Factor IX antibody, 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.

Factor IX: Difference between revisions

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@@ Line 134: / Line 134: @@
 The Gla domain perhaps also interacts with factor VIIIa via Mg2+-binding sites. Membrane bound FIXa forms an arched structure which is seen in the spatial relationship among the Gla, epidermal growth factor, and serine protease domains. This arched allows for the formation of a concave surface on the right side of FIXa  and acts as a binding site for factor VIIIa. The Mg-8 ion points toward this concave surface making it ideal in the interaction between FIXa and GVIIIa. Similarly, [[Mg-8 may contribute to the binding to factors VIIa and X]].
+Bovine Factor IX-(1-46) bound to a snake venom protein (Factor IX-bp), is crystallized in the presence of calcium and magnesium ions and in the presence of calcium alone.
+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).
+To further probe into the structure of FIX Gla domain, conformation-specific anti-Factor IX antibodies were utilized. Using an anti-Factor IX antibody, 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.