Regulation of thrombus formation by modulating platelet-von Willebrand factor interaction

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461463
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Fujita Health University
• Principal Investigator: MATSUI Taei 藤田保健衛生大学, 保健学研究科, 教授 (90183946)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: フォン・ビルブランド因子 / 血小板 / GPIb / ボトロセチン2 / 血小板凝集 / 抗血栓 / 組換えタンパク質

Outline of Final Research Achievements

Platelet plug formation is triggered by the early interaction between platelet GPIb and von Willebrand factor (VWF). I have focused on the structure and function of botrocetin2, the snake venom derived protein that specifically binds to VWF and induces GPIb-dependent platelet agglutination. I have elucidated important residues of botrocetin2 for binding to VWF and GPIb, respectively. By substituting basic two residues of botrocretin2 that are important for GPIb-binding to acidic residues, this mutant botrocetin2 showed no agonist activity for platelet agglutination, conversely, it deprived VWF of platelet agglutinability. Present results suggest the possibility that this mutant botrocetin2 may lead to an anti-thrombus reagent specifically targeting VWF.

Free Research Field

血栓止血学