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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 血小板膜糖蛋白(GP)Ibalpha与固定在血管壁上的von Willebrand因子(VWF)结合可启动血栓形成。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1500 S^(-1)或更高的切变率下，血小板与细胞外基质成分的结合和血栓的生长依赖于GP Ibalpha与vWF A1结构域的结合。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 Ibalpha上的铂-MAD数据，模型的建立正在进行中。我们正在结晶GP Ibalpha与A1结构域和调节剂Botrocetin的络合物。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) Ibalpha 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 Ibalpha 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 Ibalpha and the model building is in progress. We are in the process of crystallizing complexes of the GP Ibalpha 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.