Blood coagulation factor XIII (FXIII) is a heterotetramer consisting of two potentially active A subunits and two protective/inhibitory B subunits. Activated form of the zymogen is a transglutaminase, which forms isopeptide crosslinks between two polypepti de chains. Main physiological function of FXIII is to stabilize fibrin by crosslinking its chains and to protect fibrin from the powerful fibrinolytic machinery. Inherited deficiency of FXIII result in severe bleeding tendency. During the the activation of plasma FXIII first thrombin cleaves the activation peptide of the N-terminal of FXIII-A, then if Ca2+ is present, the B subunits dissociate from the A subunits and the active-site cysteine becomes available. Synthesis site for FXIII-A is in the components of monocyte/macrophage system and in the megakaryocytes. FXIII-B is synthesized in the liver. The only known biological function of FXIII-B is the binding of FXIII-A. FXIII-B has a typical domain structure, it is composed of so-called Sushi domains. Prote ins containing Sushi domains are involved in protein-protein binding, like the different components of the complement system. Binding of the two subunits of FXIII is important to maintain the stability of FXIII-A in blood plasma environment. Without FXIII-B, FXIII-A is unstable in the blood plasma. Hardly anything is known about the details of the binding of the two subunits. The resistance and stability of the fibrin clot is a central issue for the clot lysis therapies. Therefore, the ability to influence FXIII activity can be very beneficial. Fine tuning of the level of circulating FXIII-A by specific blocking peptides or monoclonal antibodies might result in more lysable fibrin clot which can be of a great importance in the treatment of thrombosis. The go al of this application would be to identify the possible binding domain(s) on FXIII-B involved in the binding to FXIII-A with the help of immunological, molecular biological, and biochemical methods.
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