Effect of Specific Cleavage of Immunoglobulin G by Plasmin on the Binding and Activation of Plasminogen

Aisina, R.B.; Mukhametova, L.I.; Gershkovich, K.B.; Yakovlev, V.N.; Goufman, E.I.; Tikhonova, N.B.

Авторы: Aisina R.B., Mukhametova L.I., Gershkovich K.B., Yakovlev V.N., Goufman E.I., Tikhonova N.B.
Журнал: Russian Journal of Bioorganic Chemistry
Том: 44
Номер: 2
Год издания: 2018
Издательство: Maik Nauka/Interperiodica Publishing
Местоположение издательства: Russian Federation
Первая страница: 210
Последняя страница: 216
DOI: 10.1134/S1068162018010028
Аннотация: An ELISA method was developed to measure the binding degree of various immunoglobulin (IgG) samples to human plasminogen. In this method, instead of the plasminogen, we have used immobilized on the surface of the plates a heavy chain of plasmin(ogen) (Pg-H), containing five ligand-binding kringle domains. Using this method, it was found that plasmin-treated IgG (IgGPm-treat) binds to immobilized Pg-H to 2.84 times stronger than intact IgG. Herewith, the control experiments showed that both IgG samples do not bind to the immobilized light chain of plasminogen (Pg-L). It was shown that 0.2 M L-lysine completely suppresses the binding of IgGPm-treat and does not affect the binding of intact IgG to immobilized Pg-H. The observed competitive displacement of IgGPm-treat from its complex with Pg-H indicates the involvement of lysine-binding sites of Pg-H in binding to IgGPm-treat. The pre-treatment of the IgG samples with carboxypeptidase B (CPB) completely abolished the binding of IgGPm-treat and did not affect the binding of intact IgG to the immobilized Pg-H, which indicates the key role of the C-terminal lysine IgGPm-treat in binding to the lysine-binding centers of plasminogen. The effect of intact IgG and IgGPm-treat on the activation rate of Glu- and Lys-forms of plasminogen (Glu-Pg and Lys-Pg) by tissue plasminogen activator (tPA) and urokinase (uPA) in buffer was studied. Intact IgG completely suppressed the activation of both forms of plasminogen under the action of tPA and uPA. The observed inhibitory effect of intact IgG, which does not bind to the heavy chain of plasminogen, is probably due to the steric hindrance that it creates for the interaction of the zymogen and the enzyme. IgGPm-treat, which through its C-terminal lysine binds to lysine-binding centers of plasminogen, accelerated the generation of plasmin from plasminogen. The stimulating effect of IgGPm-treat on Glu-Pg activation was more pronounced than on the activation of Lys-Pg under the action of both activators, which is explained by the more significant conformational changes in the Glu-Pg molecule, compared to the Lys-Pg molecule, after their binding to IgGPm-treat. The results obtained in this study suggest that the plasminogen / plasmin system can be involved in the functioning of IgG in various pathological processes.
Добавил в систему: Мухаметова Лилия Инилевна

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