ABSTRACT
Plasma fibrin-stabilizing factor (pFXIII) is one of the key proteins of blood coagulation. The function of pFXIII is to maintain a hemostasis by the fibrin clot stabilization accompanied by its increasing mechanical strength and the enhanced resistance of the fibrin clot to plasmin. Its reference interval in the human blood plasma equals to 14-28 μg/ml [1]. It is a heterotetramer (FXIII-A2B2) with the molecular weight of 320 kDa consisting of the two single-stranded catalytic A subunits (FXIII-A2) with the molecular weight of subunit of ~83 kDa and the two identical single-stranded inhibitory/carrier B subunits (FXIII-B2) with the molecular weight of the subunit of ~73 kDa. The subunits are held together by weak non-covalent bonds [2, 3]. The pFXIII activation is a multistage process. The first stage is the thrombin-catalyzed hydrolytic cleavage of an Arg37-Gly38 bond from the amino-terminus of the FXIII-A subunit, this leads to a release of the activation peptide AP. FXIII-A2B2 transforms into FXIII-A2´B2 which still does not have an enzymatic activity [4]. The second stage of the activation requires calcium ions. In the presence of the calcium ions the heterosubunits dissociate with the formation of FXIII-A2´ and FXIII-B2. At the last stage FXIII-A2´undergoes conformational changes in the presence of Са
2+, this leads to the Cys314 active site exposure accompanied by the formation of the enzyme FXIII-A2*(FXIIIа) which belongs to the family of the transglutaminases (endo-γ-glutamine: ε-lysine transferases, EC2.3.2.13) [5]. In the presence of FXIIIа and calcium ions, fibrin polymers undergo interchain covalent crosslinking by generation of the ε-(γ-glu)lys isopeptide bonds [6]. СООН-terminal sites of γ chains located in the D peripheral regions of the monomeric fibrin molecules are covalently bound to each other to form the intermolecular γ-γ-dimers [7]. Factor XIIIа also catalyses a formation of the isopeptide bonds between α chains of neighbour fibrin molecules. In the sequence of this α chain of one molecule interacts with α chain of two other molecules what leads to appearance of α-polymers which include more than five α fibrin polypeptide chains [8]. FXIIIа is able to engage fibrin α chains to the covalent linking with other proteins such as α2-antiplasmin and fibronectin [9]. Today, the catalytic function of FXIII-A2*has been studied sufficiently well, whereas the role of the noncatalytic FXIII-B subunits is not as clear. These subunits are supposed to
be carriers of the catalytic FXIII-A subunits in the bloodstream and protect them against possible proteolytic degradation maintaining a proper level of zymogen in the bloodstream in the same way [10, 11]. Besides, the aforementioned FXIII-B subunits perform a regulatory function controlling the process of the FXIII-A2B2 activation by thrombin [12, 13].
