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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。血小板膜糖蛋白Ib？血管性假血友病因子(VWF)被固定在血管壁上，引发血栓形成。这一过程对止血是必不可少的，也可能导致血栓性疾病，如心肌梗死，并受vWF与血小板的亲和力调节。在切变率为1500 S-1或更高时，血小板与细胞外基质成分的结合和血栓的生长依赖于GP Ib？与vWF A1结构域结合。我们已经确定了vWF的A1结构域的晶体结构和A1结构域功能的调节物-蛇毒蛋白Botrocetin。现在我们已经收集了血小板膜受体GP Ib？模型建造正在进行中。我们正在结晶GP Ib？与A1结构域和调节剂Botrocetin结合。2.对细菌磷传递蛋白进行了研究。最近，我们从枯草杆菌中解开了转录因子Spo0A的结构，与含有识别序列的DNA双链形成了复合体。转录因子与其他启动子序列的复合体的结晶正在进行中。Spo0A启动产孢量。炭疽病由炭疽杆菌引起，其转录因子与枯草杆菌的转录因子几乎完全相同。

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.