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

Background: Fibrinogen is a large polyfunctional plasma protein consisting of a number of structural and functional domains. Among them, two αC-domains, each formed by the amino acid residues Аα392–610, are involved in fibrin polymerization, activation of fibrinolysis, platelet aggregation, and interaction with different cell types. Previous study revealed that each fibrinogen αC-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 desAα505–610 and fibrinogen desAα414–610, 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 αC-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.

Y.M. Stohnii, T.A. Yatsenko, V.V. Nikulina, Y.P. Kucheriavyi, O.O. Hrabovskyi, O.Yu. Slominskyi, K.S. Savchenko, L.V. Garmanchuk, L.D. Varbanets, A.O. Tykhomyrov, V.O. Chernyshenko. Functional properties of individual sub-domains of the fibrin(ogen) αC-domains. BBA Advances. 2023, Volume 3, 100072, https://doi.org/10.1016/j.bbadva.2023.100072