Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 287 (3), 452-464

Proteolytic and Nonproteolytic Activation Mechanisms Result in Conformationally and Functionally Different Forms of Coagulation Factor XIII A

Affiliations

Proteolytic and Nonproteolytic Activation Mechanisms Result in Conformationally and Functionally Different Forms of Coagulation Factor XIII A

Boris A Anokhin et al. FEBS J.

Abstract

Factor XIIIA (FXIIIA) is a transglutaminase that cross-links intra- and extracellular protein substrates. FXIIIA is expressed as an inactive zymogen, and during blood coagulation, it is activated by removal of an activation peptide by the protease thrombin. No such proteolytic FXIIIA activation is known to occur in other tissues or the intracellular form of FXIIIA. For those locations, FXIIIA is assumed instead to undergo activation by Ca2+ ions. Previously, we demonstrated a monomeric state for active FXIIIA. Current analytical ultracentrifugation and kinetic experiments revealed that thrombin-activated FXIIIA has a higher conformational flexibility and a stronger affinity toward glutamine substrate than does nonproteolytically activated FXIIIA. The proteolytic activation of FXIIIA was further investigated in a context of fibrin clotting. In a series of fibrin cross-linking assays and scanning electron microscopy studies of plasma clots, the activation rates of FXIIIA V34X variants were correlated with the extent of fibrin cross-linking and incorporation of nonfibrous protein into the clot. Overall, the results suggest conformational and functional differences between active FXIIIA forms, thus expanding the understanding of FXIIIA function. Those differences may serve as a basis for developing therapeutic strategies to target FXIIIA in different physiological environments. ENZYMES: Factor XIIIA ( EC 2.3.2.13).

Keywords: analytical ultracentrifugation; factor XIII; fibrin clot; scanning electron microscopy; transglutaminase.

Similar articles

See all similar articles

References

    1. Komaromi I, Bagoly Z & Muszbek L (2011) Factor XIII: novel structural and functional aspects. J Thromb Haemost 9, 9-20.
    1. Muszbek L, Bereczky Z, Bagoly Z, Komaromi I & Katona E (2011) Factor XIII: a coagulation factor with multiple plasmatic and cellular functions. Physiol Rev 91, 931-972.
    1. Schroeder V & Kohler HP (2016) Factor XIII: structure and Function. Semin Thromb Hemost 42, 422-428.
    1. Eckert RL, Kaartinen MT, Nurminskaya M, Belkin AM, Colak G, Johnson GV & Mehta K (2014) Transglutaminase regulation of cell function. Physiol Rev 94, 383-417.
    1. Hoac B, Nelea V, Jiang W, Kaartinen MT & McKee MD (2017) Mineralization-inhibiting effects of transglutaminase-crosslinked polymeric osteopontin. Bone 101, 37-48.

LinkOut - more resources

Feedback