Non-enzymatic activation of prothrombin induced by interaction with fibrin β26-42 region

In collaboration with the Department of Protein Structure and Functions of Palladin Biochemistry Institute of NAS of Ukraine we have predicted binding mode of β26-44 fibrin fragment with prethrombin. Our results were published in Acta Biochimica Polonica.

Abstract: We have discovered that addition of monomeric desAB fibrin to prothrombin leads to appearence of thrombin-like activity of prothrombin towards S2238 chromogenic substrate. DesA and desABβ(15-42)2 fibrin forms did not cause any activation of prothrombin. From this observation we could suggested that amino acid residues of the 15-42 fragment of BβN-domain presented in desAB fibrin, cleaved in desABβ(15-42)2 fibrin and protected in desA fibrin, play a crucial role in the non-enzymatic activation of prothrombin. To identify the Bβ amino acid residues involved in the fibrin-prothrombin binding we used monoclonal antibodies 1-5G and 2d2a with epitopes in Bβ26-42 and Bβ12-26 fibrin fragments respectively. The thrombin-like activity in the mixture of prothrombin and desAB fibrin was monitored in the presence of each of these monoclonal antibodies. It was found that anti-Bβ12-26 antibody does not exhibit any inhibitory effect on the thrombin-like activity of the mixture. In contrast, adding of Bβ26-42 antibody into the mixture of desAB fibrin with prothrombin diminished the thrombin-like activity by 70%. Recombinant dimeric peptides Bβ(15-44)2 and Bβ(15-66)2 that mimic amino acid residues in fibrin were also tested for their ability to activate prothrombin. It was found that both peptides were able to induce non-enzymatic activation of prothrombin. The activation was more evident in the case of Bβ(15-44)2 peptide. From the data obtained we can conclude that desAB fibrin binds to prothrombin trough the Bβ26-42 amino acid residues and the formation of such a complex caused a non-enzymatic activation of prothrombin.    

• Non-enzymatic activation of prothrombin induced by interaction with fibrin β26-42 region. Chernyshenko VO, Chernyshenko TM, Korolova DS, Volynets GP, Kolesnikova IN, Platonova TM, Lugovskoy EV. Acta Biochimica Polonica. 2025, 62:517-522.