Heparin inhibits the binding of beta 2-glycoprotein I to phospholipids and promotes the XXXX -mediated inactivation of this blood protein. Elucidation of the consequences of the two biological events in @entity1 with the @entity1701 .

@entity1 @entity9500 @entity1351 @entity1701
The phospholipid-binding plasma protein @entity9500 ( @entity9500 ) is the primary antigen recognized by the circulating autoantibodies in @entity1 with the " @entity1701 " ( @entity1701 ). Although heparin is routinely used in the treatment and prophylaxis of @entity1701 @entity1 , the primary heparin-binding site within @entity9500 has not been identified. More importantly, how heparin exerts its beneficial effects in vivo in @entity1701 @entity1 has not been deduced at the molecular level. Using an expression/site-directed mutagenesis approach, we now show that the positively charged site that resides in the first domain of @entity9500 is not the primary heparin-binding site. Rather it is the second positively charged site located within the fifth domain of the protein that also binds to phospholipids. Lys(284), Lys(286), and Lys(287) in this domain are essential for the interaction of @entity9500 with heparin. These data indicate that @entity9500 binds to heparin in a relatively specific manner even though the affinity for the interaction is rather low. Lys(317) resides in the center of the high affinity phospholipid-binding site. Surprisingly, heparin at concentrations that can be achieved in vivo during anticoagulation therapy greatly enhances the @entity1351 -mediated cleavage of the Lys(317)-Thr(318) site in @entity9500 . Because the cleaved form cannot bind to phospholipids effectively, the combined actions of heparin and @entity1351 result in a diminished ability of @entity9500 to recognize phospholipids. This, in turn, decreases the prothrombotic activity of the endogenous circulating anti- @entity9500 antibodies in the @entity1 . Thus, heparin exerts its beneficial effects in @entity1701 @entity1 by at least two distinct mechanisms.
