CRYSTAL STRUCTURE OF VON WILLEBRAND FACTOR AL DOMAIN

我们希望使用同步加速器辐射技术来确定 人类血管性血友病因子 (vWF) A1 结构域的 3D 结构。 从该项目中获得的信息将有助于澄清 正常运行所必需的关键事件的机制和调节 止血并参与病理性血栓形成。 目前认为天然 vWF 的结晶是不可能的 由于大尺寸和异质性，可用技术 分子；因此，这是获取 3D 信息的唯一方法 vWF的结构是专注于孤立的域。 结果 我们的研究预计将有助于定义 vWF-GP Ib 接触 位点并将协助寻找 vWF 的特异性抑制剂 与 GP Ib 结合，是抗血栓的重要靶点 干预。

We wish to use synchrotron radiation techniques to determine the 3D structure of the A1 domain of human von Willebrand factor (vWF). The information gained from this project will help clarify the mechanisms and regulation of a key event essential for normal hemostasis and also involved in pathological thrombosis. Crystallization of native vWF is considered impossible with currently available techniques due to the large size and heterogeneous nature of the molecule; thus the only approach to gain information on the 3D structure of vWF is to focus on isolated domains. The results expected from our studies will help in defining the vWF-GP Ib contact sites and will assist in searching for specific inhibitors of vWF binding to GP Ib, an important target for anti-thrombotic intervention.