Oxidative Modification of Coagulation Factor XIII: Structural and Functional Aspects

A. D. Vasilyeva, L. V. Yurina, V. B. Leonova, D. Yu Azarova, A. E. Bugrova, T. S. Konstantinova, M. I. Indeykina, Alexey Kononikhin, E. N. Nikolaev, M. A. Rosenfeld

    Результат исследований: Вклад в журналСтатьярецензирование

    5 Цитирования (Scopus)

    Аннотация

    Abstract—: The plasma coagulation factor XIII (рFXIII) is a key protein of the blood coagulation systems, the main function of which consists of the enzymatic covalent stabilization of the polymeric structure of fibrin. The protein has a heterotetrameric structure consisting of two catalytic (FXIII-A2) and two regulatory (FXIII-В2) subunits. Using a high resolution mass spectrometry, hypochlorite-induced oxidation of рFXIII molecules and its enzymatic form (FXIIIa) is studied for the first time. It is demonstrated that sulfur and aromatic amino acid residues are the most vulnerable residues to oxidative attack. The mass spectrometry data indicate that oxidized amino acid residues are found in all structural elements of the FXIII-A catalytic subunit in the protein we are studying (except for the activation peptide), while a number of domains remain in native form in the FXIII-В regulatory subunit. When treated FXIIIa with hypochlorite, additional modification sites both in the FXIII-A*2 and in the FXIII-В2 subunits are detected. The data obtained allowed us to postulate that in the process of converting the proenzyme into FXIIIa, new amino acid residues (previously inaccessible to oxidizers) migrate to the surface of the protein globule and become vulnerable targets for oxidizer molecules, while some of the initially surface-exposed amino acid residues move inside the protein, losing their ability to participate in the oxidative modifications. Electrophoresis of reduced samples of covalently cross-linked fibrin detected a decrease in transglutaminase activity of oxidized FXIIIa manifested in the inhibition of the reaction of the formation of γ–γ-dimers. The ability of the рFXIII molecule to resist the oxidative attack due to its antioxidant structural adaptation to the effect of reactive oxygen species is discussed.

    Язык оригиналаАнглийский
    Страницы (с-по)468-478
    Число страниц11
    ЖурналRussian Journal of Physical Chemistry B
    Том14
    Номер выпуска3
    DOI
    СостояниеОпубликовано - 1 мая 2020

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