The structure of blood coagulation factor xiii is adapted to oxidation

Alexandra Vasilyeva, Lyubov Yurina, Alexander Shchegolikhin, Maria Indeykina, Anna Bugrova, Alexey Kononikhin, Eugene Nikolaev, Mark Rosenfeld

    Research output: Contribution to journalArticlepeer-review

    3 Citations (Scopus)

    Abstract

    The blood coagulation factor XIII (FXIII) plays a critical role in supporting coagulation and fibrinolysis due to both the covalent crosslinking of fibrin polymers, rendering them resistant to plasmin lysis, and the crosslinking of fibrin to proteins of the fibrinolytic system. The hypochlorite-mediated oxidation of the blood coagulation factor XIII (FXIII) at the different stages of its enzymatic activation is studied for the first time in this paper. The consolidated results obtained with the aid of MS/MS, electrophoresis, and colorimetry demonstrate that in the process of FXIII’s conversion into FXIIIa, the vulnerability of FXIII to hypochlorite-induced oxidation increased as follows: native FXIII < FXIII + Ca2+ << FXIII + Ca2+/thrombin. The modification sites were detected among all the structural regions of the catalytic FXIII-A subunit, except for the activation peptide, and embraced several sushi domains of the FXIII-B subunit. Oxidized amino acid residues belonging to FXIII-A are surface-exposed residues and can perform an antioxidant role. The regulatory FXIII-B subunits additionally contribute to the antioxidant defense of the catalytic center of the FXIII-A subunits. Taken together, the present data along with the data from previous studies demonstrate that the FXIII proenzyme structure is adapted to oxidation.

    Original languageEnglish
    Article number914
    Pages (from-to)1-17
    Number of pages17
    JournalBiomolecules
    Volume10
    Issue number6
    DOIs
    Publication statusPublished - Jun 2020

    Keywords

    • Blood coagulation factor XIII (FXIII)
    • HPLC-MS/MS
    • Hypochlorite-induced oxidation
    • Oxidative modifications
    • Reactive oxygen species (ROS)
    • Structural adaptation

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