The collagen-binding integrin α2β1 is a novel interaction partner of the Trimeresurus flavoviridis venom protein flavocetin-A.

摘要: Many snake venoms are known for their antithrombotic activity. They contain components that specifically target different platelet-activating receptors such as the collagen-binding integrin α2β1 and von Willebrand factor receptor GPIb. In a search an integrin-blocking component from venom of habu (Trimeresurus flavoviridis), we employed two independent purification protocols. First, used α2A domain, major bait affinity integrin-binding toxin crude venom. Second, in parallel, classical protein separation protocols tested integrin-inhibiting capabilities by ELISA. Using both approaches, identified flavocetin-A inhibitor integrin. Hitherto, has been reported GPIb inhibitor. However, inhibited collagen-induced platelet aggregation even after was blocked with other inhibitors. Moreover, antagonized integrin-mediated adhesion migration HT1080 human fibrosarcoma cells, which lack any GPIb, on collagen. Protein chemical analyses proved binds to its domain high cooperative manner, most likely is due quaternary structure. Kinetic measurements confirmed formation strong complex between flavocetin-A, dissociates very slowly. This study proves long inhibitor, efficiently targets thus blocks activation. our findings suggest GPIb- members within C-type lectin-related family less strict than previously assumed.