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

冯·威勒布兰德因子复合物的 A1 域；

• 批准号: 7721736
• 负责人: KOTTAYIL I VARUGHESE
• 金额: $ 0.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721736
• 关键词: Affinity; Anthrax disease; Bacillus anthracis; Binding; Blood Platelets; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallization; DNA; Data; Disease; Extracellular Matrix; Funding; Glycoproteins; Grant; Growth; Hemorrhage; Institution; Membrane; Modeling; Myocardial Infarction; Platelet Membrane Glycoproteins; Process; Proteins; Rate; Research; Research Personnel; Resources; Signal Transduction; Site; Snake Venoms; Source; Structure; Thrombus; United States National Institutes of Health; botrocetin; promoter; receptor; transcription factor; von Willebrand Factor; wound

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 血小板膜糖蛋白 (GP) Ibalpha 与固定在血管壁上的血管性血友病因子 (vWF) 的结合引发血栓形成。 这一过程对于伤口部位止血至关重要，也可能导致心肌梗塞等血栓性疾病，并且受 vWF 对血小板的亲和力调节。 在 1500 s^(-1) 或更高的壁剪切速率下，血小板与细胞外基质成分的束缚和血栓生长取决于 GP Ibalpha 与 vWF A1 结构域的结合。 我们已经确定了 vWF A1 结构域和 A1 结构域功能调节剂——蛇毒蛋白 Botrocetin 的晶体结构。 目前我们已经收集了血小板膜受体GP Ibalpha的Pt MAD数据，模型构建正在进行中。我们正在结晶 GP Ibalpha 与 A1 结构域和调节剂 botrocetin 的复合物。 2.研究细菌磷酸中继蛋白。 最近，我们解析了来自枯草芽孢杆菌的转录因子 Spo0A 与含有识别序列的 DNA 双链体的复合物的结构。 与其他启动子序列复合的转录因子的结晶正在进行中。 Spo0A 启动孢子形成。 炭疽病是由炭疽芽孢杆菌引起的，其转录因子与枯草芽孢杆菌几乎相同。