Structure functional insights into calcium binding during the activation of coagulation factor XIII A.

The dimeric FXIII-A, a pro-transglutaminase is the catalytic part of the heterotetrameric coagulation FXIII-AB complex that upon activation by calcium binding/thrombin cleavage covalently cross-links preformed fibrin clots protecting them from premature fibrinolysis. Our study characterizes the recently disclosed three calcium binding sites of FXIII-A concerning evolution, mutual crosstalk, thermodynamic activation profile, substrate binding, and interaction with other similarly charged ions. We demonstrate unique structural aspects within FXIII-A calcium binding sites that give rise to functional differences making FXIII unique from other transglutaminases.