Functional properties of individual sub-domains of the fibrin(ogen) α C-domains

Background: Fibrinogen is a large polyfunctional plasma protein consisting of a number of structural and functional domains. Among them, two alpha C-domains, each formed by the amino acid residues & Acy; alpha 392-610, are involved in fibrin polymerization, activation of fibrinolysis, platelet aggregation, and interaction with different cell types. Previous study revealed that each fibrinogen alpha C-domain consists of the N -terminal and C -terminal sub -domains. The major objections of the present study were to test functional role of these sub -domains in the above mentioned processes. Methods: To achieve these objections, we used specific proteases to prepare two truncated forms of fibrinogen, fibrinogen desA alpha 505-610 and fibrinogen desA alpha 414-610, missing their N -terminal and both N- and C -terminal sub -domains, respectively. Results: Our study with these truncated forms using turbidity measurements and electron microscopy revealed that the N- and C -terminal subdomains both contribute to protofibril formation and their lateral aggregation into fibers during fibrin polymerization process. These two sub -domains also contributed to platelet aggregation with the N -terminal sub -domains playing a more significant role in this process. At the same time, the C -terminal subdomains make the major contribution to the plasminogen activation process. Further, our experiments revealed that the C -terminal sub -domains are involved in endothelial cell viability and migration of cancer cells. Conclusions: Thus, the results obtained establish the functional role of individual sub -domains of the alpha C-domains in fibrin polymerization, activation of fibrinolytic system, platelet aggregation, and cellular interactions. General significance: The present study expands our understanding of the functional role of individual fibrinogen domains and their specific portions in various fibrin(ogen)-dependent processes.