Alpha-chain domain of fibrinogen controls generation of fibrinoligase (coagulation factor XIIIa). Calcium ion regulatory aspects.

Fibrinogen (approximately 10(-5) M) labilizes heterologous interactions within the thrombin-modified factor XIII zymogen (i.e., XIII' = a2'b2) so that, in the time frame (ca. 10 min) of normal clotting in plasma (37 degrees C, mu = 0.15, pH 7.5), 1.5 mM Ca2+ is sufficient to cause the release of the noncatalytic b subunits and also the unmasking of 1 equiv of iodo[1-14C]acetamide-titratable group per catalytic a subunit. Under similar conditions, but in the absence of fibrinogen, approximately 10 mM Ca2+ would be needed to achieve the same effect. Thus, by promoting the conversion of XIII' to XIIIa (i.e., a2'b2 leads to a2* + b2), fibrinogen functions as a physiologically important Ca2+-modulator protein. Total plasmin digests of fibrinogen display the regulatory phenomenon nearly as well as the parent protein. In an attempt to identify the structural domain on the fibrinogen which is responsible for this novel function of the molecule, it was found that two overlapping fragments derived from the midsections of the alpha chains, either by CNBr cleavage (residues 243-476) or by plasmin digestion (residues 242-424), are active.