An αIIb β3 - and phosphatidylserine (PS)-binding recombinant fusion protein promotes PS-dependent anticoagulation and integrin-dependent antithrombosis

The Journal of Biological Chemistry
Jian Jing, Yanna Sun

Abstract

Blood platelets are required for normal wound healing, but they are also involved in thrombotic diseases, which are usually managed with anticoagulant drugs. Here, using genetic engineering, we coupled the disintegrin protein echistatin, which specifically binds to the platelet integrin αIIbβ3 receptor, to annexin V, which binds platelet membrane-associated phosphatidylserine (PS), to create the bifunctional antithrombotic molecule recombinant echistatin-annexin V fusion protein (r-EchAV). Lipid binding and plasma coagulation studies revealed that r-EchAV dose-dependently binds PS and delays plasma clotting time. Moreover, r-EchAV inhibited ADP-induced platelet aggregation in a dose-dependent manner and exhibited potent antiplatelet aggregation effects. r-EchAV significantly prolonged activated partial thromboplastin time, suggesting that it primarily affects the in vivo coagulation pathway. Flow cytometry results indicated that r-EchAV could effectively bind to the platelet αIIbβ3 receptor, indicating that r-EchAV retains echistatin's receptor-recognition region. In vivo experiments in mice disclosed that r-EchAV significantly prolongs bleeding time, indicating a significant anticoagulant effect in vivo resulting from the join...Continue Reading

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Citations

Mar 8, 2020·Journal of Thrombosis and Haemostasis : JTH·Moeka NakayamaKyoko Kojima-Aikawa
Jul 2, 2020·Drug Design, Development and Therapy·Asad Majeed KhanSana Shafique
Apr 4, 2021·International Journal of Molecular Sciences·Thomas GrewalUrsula Rescher

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