X-ray crystal structure of the fibrinolysis inhibitor α2-antiplasmin

Abstract

The serpin α2-antiplasmin (SERPINF2) is the principal inhibitor of plasmin and inhibits fibrinolysis. Accordingly, α2-antiplasmin deficiency in humans results in uncontrolled fibrinolysis and a bleeding disorder. α2-antiplasmin is an unusual serpin, in that it contains extensive N-and C-terminal sequences flanking the serpin domain. The N-terminal sequence is crosslinked to fibrin by factor XIIIa, whereas the C-terminal region mediates the initial interaction with plasmin. To understand how this may happen, we have determined the 2.65Å X-ray crystal structure of an N-terminal truncated murine α2-antiplasmin. The structure reveals that part of the C-terminal sequence is tightly associated wit..