Single-chain factor XII

A new form of activated factor XII

Ivan Ivanov, Anton Matafonov, David Gailani

    Research output: Contribution to journalReview article

    5 Citations (Scopus)

    Abstract

    Exposure of blood to foreign surfaces induces reciprocal conversion of the plasma proteins factor XII (fXII) and plasma prekallikrein (PPK) to the proteases α-fXIIa and α-kallikrein. This process, called contact activation, has a range of effects on host defence mechanisms, including promoting coagulation. The nature of the triggering mechanism for contact activation is debated. One hypothesis predicts that fXII has protease activity, either intrinsically or upon surface-binding, that initiates contact activation. We tested this by assessing the proteolytic activity of a recombinant fXII variant that cannot be converted to α-fXIIa. Recent findings The proteolytic activity of fXII-T (for 'triple' mutant), a variant with alanine substitutions for arginine at activation cleavage sites (Arg334, Arg344, and Arg353) was tested with known α-fXIIa substrates. FXII-T activates PPK in solution, and the reaction is enhanced by polyphosphate, an inducer of contact activation released from platelets. In the presence of polyphosphate, fXII-T converts fXII to α-fXIIa, and also converts the coagulation protein factor XI to its active form. Summary: The findings support the hypothesis that contact activation is initiated through activity intrinsic to single-chain fXII, and indicate that preexisting α-fXIIa is not required for induction of contact activation.

    Original languageEnglish
    Pages (from-to)411-418
    Number of pages8
    JournalCurrent Opinion in Hematology
    Volume24
    Issue number5
    DOIs
    Publication statusPublished - 1 Sep 2017

    Fingerprint

    Factor XIIa
    Factor XII
    Prekallikrein
    Polyphosphates
    Peptide Hydrolases
    Factor XI
    Kallikreins
    Platelet Activation
    Alanine
    Arginine
    Blood Proteins

    Keywords

    • contact activation
    • factor XI
    • factor XII
    • plasma prekallikrein

    ASJC Scopus subject areas

    • Hematology

    Cite this

    Single-chain factor XII : A new form of activated factor XII. / Ivanov, Ivan; Matafonov, Anton; Gailani, David.

    In: Current Opinion in Hematology, Vol. 24, No. 5, 01.09.2017, p. 411-418.

    Research output: Contribution to journalReview article

    Ivanov, Ivan ; Matafonov, Anton ; Gailani, David. / Single-chain factor XII : A new form of activated factor XII. In: Current Opinion in Hematology. 2017 ; Vol. 24, No. 5. pp. 411-418.
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