Oxidation-induced modifications of the catalytic subunits of plasma fibrin-stabilizing factor at the different stages of its activation identified by mass spectrometry

Alexandra Vasilyeva, Lyubov’ Yurina, Maria Indeykina, Anna Bychkova, Anna Bugrova, Marina Biryukova, Alexey Kononikhin, Evgene Nikolaev, Mark Rosenfeld

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    13 Citations (Scopus)

    Abstract

    Plasma fibrin-stabilizing factor (pFXIII) is a heterotetrameric proenzyme composed of two catalytic A subunits (FXIII-A2) and two inhibitory/carrier B subunits (FXIII-B2). The main function of the protein is the formation of cross-links between the polypeptide chains of the fibrin clot. The conversion of pFXIII into the enzymatic form FXIII-A2* is a multistage process. Like many other blood plasma proteins, pFXIII is an oxidant-susceptible target. The influence of distinct sites susceptible to oxidation-mediated modifications on the changes in the structural-functional characteristics of the protein remains fully unexplored. For the first time, a set of the oxidation sites within FXIII-A2 under ozone-induced oxidation of pFXIII at different stages of its activation have been identified by mass spectrometry, and the extent as well as the chemical nature of these modifications have been explored. It was shown that the set of amino acid residues susceptible to oxidative attack and the degree of oxidation of these residues in FXIII-A2 of non-activated pFXIII, pFXIII activated by Ca2+ and fully activated pFXIII treated with thrombin and Ca2+ significantly differ. The obtained data enable one to postulate that in the process of the proenzyme conversion into FXIII-A2* new earlier-unexposed amino acid residues become available for the oxidizer while some of the initially surface-exhibited residues are buried within the protein globule.

    Original languageEnglish
    Pages (from-to)875-884
    Number of pages10
    JournalBiochimica et Biophysica Acta - Proteins and Proteomics
    Volume1866
    Issue number8
    DOIs
    Publication statusPublished - Aug 2018

    Keywords

    • Fibrin-stabilizing factor
    • Mass spectrometry
    • Oxidative modifications
    • Reactive oxygen species (ROS)

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