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

Publisher Website
Google Scholar
Abstract
Human fibrinogen (.apprx. 10-5 M) labilizes heterologous interactions within the thrombin-modified factor XIII zymogen (i.e., XIII'' = a2''b2) so that, in the time frame (.apprx. 10 min) of normal clotting in plasma (37.degree. C, .mu. = 0.15, pH 7.5), 1.5 mM Ca2+ is sufficient to cause the release of the noncatalytic b subunits and the unmasking of 1 eq of iodo[1-14C]acetamide-titratable group per catalytic a subunit. Under similar conditions, but in the absence of fibrinogen, .apprx. 10 mM Ca2+ would be needed to achieve the same effect. By promoting the conversion of XIII'' to XIIIa, 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. Concerning the structural domain on the fibrinogen which is responsible for this novel function of the molecule, 2 overlapping fragments derived from the midsections of the .alpha. chains, either by CNBr cleavage (residues 243-476) or by plasmin digestion (residues 242-424), apparently are active.