The zymogen forms of blood coagulation factor XIII bind specifically to fibrinogen.
To examine the possibility that Factor XIII zymogens bind to fibrinogen, we have studied the reaction between radiolabeled Factor XIII and fibrinogen coupled to beads. Platelet and plasma Factor XIII were iodinated with Na(125I)iodide using lactoperoxidase. Both forms of 125I-Factor XIII retained greater than 92% of the transglutaminase activity. 125I-platelet and plasma Factor XIII specifically bound to human fibrinogen covalently coupled to either carboxylated latex or acrylonitrile beads but not to fetuin- or albumin-coated beads. Unlabeled platelet Factor XIII inhibited 90% of the total binding of 125I-platelet and 125I-plasma Factor XIII to fibrinogen, whereas human IgG, fetuin, and serum albumin had no effect. These data suggest that 125I-platelet and plasma Factor XIII specifically bind to fibrinogen by the a2 subunit. 125I-Factor XIII which was bound to the fibrinogen beads migrated identically to unbound material on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Soluble fibrinogen inhibited binding of 125I-Factor XIII to fibrinogen beads, indicating that binding is not due to alteration of the fibrinogen coupled to the beads. Binding of 125I-Factor XIII was reversible and time- and temperature-dependent: maximal binding occurred by 1 min at 37 degrees C. Binding was independent of calcium; 10 mM EDTA had no effect. Binding was dependent on sodium chloride concentration; complete inhibition of binding occurred at concentrations above 300 mM NaCl. The Kd for binding, 1 X 10(-8) M, is approximately 7-fold higher than the concentration of Factor XIII in plasma. These data support the hypothesis that Factor XIII circulates in plasma bound to fibrinogen. This interaction may play a role in regulating the physiologic activation and function of Factor XIII.
D001792:Blood Platelets / Q000201:enzymology; D005176:Factor XIII / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007840:Latex; D011485:Protein Binding; D013696:Temperature
D007840:Latex; D005340:Fibrinogen; D005176:Factor XIII