A1 DOMAIN OF VON WILLEBRAND FACTOR COMPLEXES; AND BACTERIAL SIGNAL TRANSDUCTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。血小板膜糖蛋白（GP） Ib？血管性血友病因子（vWF）固定在血管壁上引发血栓形成。这一过程对伤口止血至关重要，但也可能导致血栓性疾病，如心肌梗死，并受vWF对血小板的亲和力调节。在1500s -1或更高的壁剪切速率下，血小板粘附到细胞外基质成分和血栓生长取决于GP Ib？绑定到vWF A1域。我们已经确定了vWF的A1结构域的晶体结构和A1结构域功能调节剂-蛇毒蛋白botrocetin。现在我们已经收集了血小板膜受体GP Ib？模型构建正在进行中。我们正处于GP Ib？A1结构域和乳素调制器。2. 研究了细菌磷接力蛋白。最近，我们用含有识别序列的DNA双工复合物解决了枯草芽孢杆菌转录因子Spo0A的结构。转录因子与其他启动子序列复合体的结晶正在进行中。Spo0A开始产孢。炭疽是由炭疽芽孢杆菌引起的，其转录因子与枯草芽孢杆菌的转录因子几乎相同。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Binding of the platelet membrane glycoprotein (GP) Ib? to von Willebrand Factor (vWF) immobilized on the vessel wall initiates thrombus formation. This process, essential to arrest bleeding at wound sites, may also contribute to thrombotic diseases such as myocardial infarction, and is modulated by the affinity of vWF for platelets. At wall shear rates of 1500 s-1 or greater, platelet tethering to extracellular matrix components and thrombus growth depend on GP Ib? binding to the vWF A1 domain. We have determined the crystal structures the A1 domain of vWF and a modulator of A1 domain function- a snake venom protein, botrocetin. Now we have collected Pt MAD data on the platelet membrane receptor GP Ib? and the model building is in progress. We are in the process of crystallizing complexes of the GP Ib? with the A1 domain and the modulator botrocetin. 2. Bacterial phosphorelay proteins are investigated. Recently we solved the structure of the transcription factor Spo0A from B. subtilis in complex with a DNA duplex containing the recognition sequence. Crystallization of the transcription factor in complex with other promotor sequences are in progress. Spo0A initiates sporulation. Anthrax is caused by B. anthracis and its transcription factor is almost identical with that of B. subtilis.