Human complement C3 is a substrate for transglutaminases. A functional link between non-protease-based members of the coagulation and complement cascades.
In this study, we report the finding of functional cross-talk between two non-protease components of the complement and coagulation cascades. We show that complement C3, a central component of the complement system, is associated with the fibrin clot and that C3 becomes covalently cross-linked to other proteins during coagulation. Enzymatic incorporation of dansylcadaverine and dansyl-PGGQQIV into C3 by coagulation factor XIIIa and tissue transglutaminase demonstrated that C3 is a transglutaminase substrate. This suggested that coagulation factor XIIIa covalently cross-links C3 to clot components during coagulation. Using mass spectrometry, we verified that C3 indeed is covalently associated with the fibrin clot in a ratio of 0.05:1 relative to the known coagulation factor XIIIa substrate α2-antiplasmin.
Department of Molecular Biology and Genetics, University of Aarhus, Aarhus C, Denmark.
Camilla Lund
CL
Nikolajsen
Carsten
C
Scavenius
Jan J
JJ
Enghild
D000595:Amino Acid Sequence; D001665:Binding Sites; D001777:Blood Coagulation / Q000502:physiology*; D002384:Catalysis; D003167:Complement Activation / Q000502:physiology*; D003176:Complement C3 / Q000378:metabolism*; D026122:Factor XIIIa / Q000378:metabolism*; D006801:Humans; D010949:Plasma; D013379:Substrate Specificity; D013927:Thrombosis; D011503:Transglutaminases / Q000378:metabolism*
D003176:Complement C3; D026122:Factor XIIIa; D011503:Transglutaminases