Interactions of factor XIII with fibrin as substrate and cofactor.
Factor XIIIa (a2') is a homodimeric transglutaminase that is formed via limited alpha-thrombin-catalyzed proteolysis of the platelet (a2) or plasma (a2b2) factor XIII zymogen in a reaction that results in proteolytic removal of a 37-aminoacyl residue peptide from the N-terminus of the a chains and exposure of the active-site thiol group in the resulting a' chains of factor XIIIa. In this study, we characterized interactions of factor XIII and factor XIIIa with fibrin, a natural substrate for factor XIIIa and a cofactor for the alpha-thrombin-catalyzed activation of plasma factor XIII. The carbamylmethyl derivatives of the active-site thiol group of platelet factor XIII (CMa2) and factor XIIIa (CMa2') were prepared, and their interactions with fibrin were measured. The enzyme-like derivative (CMa2') which contained nicked a' chains bound more tightly to fibrin (Kd = 2.1 microM) than did CMa2 (Kd = 14 microM), the platelet zymogen-like derivative with intact a chains, but the binding of each was weaker than the binding of plasma factor XIII zymogen (a2b2) to fibrin (Kd = 0.20 microM) under the same conditions. Saturation of fibrin with plasma factor XIII zymogen (a2b2) did not affect the binding of CMa2' to fibrin, suggesting that the plasma factor XIII zymogen (a2b2) and the active-site-modified form of factor XIIIa (CMa2') bind to separate, noninteracting sites of fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)
Hornyak
T J
TJ
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109-0606.
Shafer
J A
JA
D001667:Binding, Competitive; D001792:Blood Platelets / Q000201:enzymology; D004347:Drug Interactions; D005174:Factor XII / Q000378:metabolism; D005176:Factor XIII / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D013379:Substrate Specificity; D013917:Thrombin / Q000378:metabolism
D005174:Factor XII; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D013917:Thrombin