1) ADHESIVE MOLECULAR INTERACTIONS IN PLATELET FUNCTION; 2) BACTERIAL SIGNALING

1) 血小板功能中的粘附分子相互作用；

• 批准号: 8170088
• 负责人: KOTTAYIL I VARUGHESE
• 金额: $ 0.13万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170088
• 关键词: Adhesives; Bacillus subtilis; Bacteria; Binding; Blood Clot; Blood Platelets; Blood coagulation; Blood flow; Complex; Computer Retrieval of Information on Scientific Projects Database; Disease; Funding; Genetic Materials; Glycoproteins; Goals; Grant; Growth; Hemorrhage; Institution; Mediating; Membrane; Molecular; Mutation; N-terminal; Play; Reproduction spores; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Structure; System; Techniques; Thrombin; Thrombus; United States National Institutes of Health; VWF gene; artery occlusion; receptor; response; von Willebrand Factor

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. (i) The interactions between the A1 domain of von Willebrand factor(VWF) and the platelet membrane receptor glycoprotein (GP) Ibalpha plays a crucial role in the arrest of bleeding where blood flow is rapid and also in the pathological thrombus formation leading to arterial occlusion. Additionally, GP Ibalpha interacts with thrombin which in turn activates platelets and regulates blood clotting. Both these interactions are mediated through the N-terminal domain of the glycoprotein (GP IbalphaN). The goal of this proposal is to study the interactions of GPIbalphaN with thrombin and vWF A1 and thrombin by crystallographic techniques. Mutations in VWF A1 and GPIbalphaN cause bleeding disorders. We are investigating the effects of these mutations on inter-molecular interactions by analyzing the crystal structures of the complexes. (ii) Bacteria use the two-component systems to adapt to changes in the environmental conditions. In response to deteriorating conditions of growth, certain types of bacteria form spores in order to preserve the genetic material until growth conditions turn favorable again. The formation of spores in Bacillus subtilis is controlled by an expanded version of the two-component system called the phosphorelay. We are carrying out crystallographic studies aimed at elucidating the mechanism of phosphorelay signaling at the molecular level.

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。子项目和 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。 (i) 血管性血友病因子 (VWF) 的 A1 结构域与血小板膜受体糖蛋白 (GP) Ibalpha 之间的相互作用在血流快速时的止血以及导致动脉闭塞的病理性血栓形成中起着至关重要的作用。此外，GP Ibalpha 与凝血酶相互作用，进而激活血小板并调节血液凝固。这两种相互作用都是通过糖蛋白 (GP IbalphaN) 的 N 末端结构域介导的。本提案的目标是通过晶体学技术研究 GPIbalphaN 与凝血酶以及 vWF A1 和凝血酶的相互作用。 VWF A1 和 GPIbalphaN 突变会导致出血性疾病。我们正在通过分析复合物的晶体结构来研究这些突变对分子间相互作用的影响。 (ii) 细菌利用双组分系统来适应环境条件的变化。为了应对日益恶化的生长条件，某些类型的细菌会形成孢子，以保存遗传物质，直到生长条件再次变得有利。枯草芽孢杆菌中孢子的形成是由称为磷酸继电器的双组分系统的扩展版本控制的。我们正在进行晶体学研究，旨在在分子水平上阐明磷酸中继信号传导机制。