Identification of heparin interaction sites on thrombin-activatable fibrinolysis inhibitor that modulate plasmin-mediated activation, thermal stability, and antifibrinolytic potential.

ABSTRACT:

Background

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen that provides a molecular link between coagulation and fibrinolysis. Studies have shown that the presence of glycosaminoglycans accelerates TAFI activation by plasmin and stabilizes activated TAFI (TAFIa).

Objectives

We aimed to define the elements of TAFI structure that allow these effects.

Methods

Based on crystallographic studies and homology to heparin-binding proteins, we performed mutagenesis of surface-exposed charged residues on TAFI that putatively constitute heparin-binding sites. We determined heparin binding, kinetics of activation by plasmin in the presence or absence of heparin, thermal stability, and antifibrinolytic potential of each variant.

Results

Mutagenesis of

SUBMITTER: Marar TT 

PROVIDER: S-EPMC11231710 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature