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

Autor:	Chernyshenko VO; Palladin Biochemistry Institute of NAS of Ukraine Kyiv, Protein Structure and Functions Department, Kyiv, Ukraine., Chernyshenko TM; Palladin Biochemistry Institute of NAS of Ukraine Kyiv, Protein Structure and Functions Department, Kyiv, Ukraine., Korolova DS; Palladin Biochemistry Institute of NAS of Ukraine Kyiv, Protein Structure and Functions Department, Kyiv, Ukraine., Volynets GP; Institute of Molecular Biology and Genetics of NAS of Ukraine, Department of Medicinal Chemistry, Kyiv, Ukraine., Kolesnikova IN; Palladin Biochemistry Institute of NAS of Ukraine Kyiv, Protein Structure and Functions Department, Kyiv, Ukraine., Platonova TM; Palladin Biochemistry Institute of NAS of Ukraine Kyiv, Protein Structure and Functions Department, Kyiv, Ukraine., Lugovskoy EV; Palladin Biochemistry Institute of NAS of Ukraine Kyiv, Protein Structure and Functions Department, Kyiv, Ukraine.
Jazyk:	angličtina
Zdroj:	Acta biochimica Polonica [Acta Biochim Pol] 2015; Vol. 62 (3), pp. 517-22. Date of Electronic Publication: 2015 Aug 28.
DOI:	10.18388/abp.2014_896
Abstrakt:	We have discovered that addition of monomeric desAB fibrin to prothrombin leads to appearance of the 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 thombin-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 through the Bβ26-42 amino acid residues and the formation of such a complex caused a non-enzymatic activation of prothrombin.
Databáze:	MEDLINE
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