Tissue-type plasminogen activator (tPA) homozygous Tyr471His mutation associates with thromboembolic disease.

ABSTRACT: Tissue-type plasminogen activator (tPA) encoded by PLAT is a major mediator that promotes fibrinolysis and prevents thrombosis. Pathogenetic mutations in PLAT associated with venous thromboembolism have rarely been reported. Here, we report the first case of a homozygous point mutation c.1411T>C (p.Y471H) in PLAT leading to thromboembolic events and conduct related functional studies. The corresponding tPA mutant protein (tPA-Y471H) and wild-type tPA (tPA-WT) were synthesized in vitro, and mutant mice (PLAT^H/H mice) were constructed. The molecular docking and surface plasmon resonance results indicated that the mutation impeded the hydrogen-bonding interactions between the protease domain of tPA and the kringle 4 domain of plasminogen, and the binding

SUBMITTER: Tao Y 

PROVIDER: S-EPMC10556205 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature