Studies on the crystal structure of clotting factors and its binding proteins.

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We have recently isolated several C-type lectin-like proteins(CLPs) with a variety of biological activities, including anticoagulant- and platelet-modulating activities. The crystal structures ofγ-carboxyglutamic acid (Gla) domains of coagulation factors X and IX have been clarified in structural studies of complexes between the Gla domains of factor X and X-bp (a venom CLP) and between the Gla domain of factor IX and IX-bp (a venom CLP). Our recent results clearly suggest that Mg^<2+> ions are required to maintain native conformation and in vivo function of factor IX Gla domain during blood coagulation.EMS16 from the venom of Echis multisquamatus binds to the collagen receptor, integrin α2β1,also known as glycoprotein(GP) Ia/IIa, and specifically inhibits collagen binding. We have reported the crystal structure of EMS16 in complex with recombinant integrin α2-I domain that plays a central role in collagen binding. The structure of the complex at 1.9 Å resolution revealed that the collagen-binding site of the α2-I domain is covered completely by the bound EMS16. This blockage by EMS16 appears to spatially inhibit collagen binding to the α2-I domain.