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: 7954415
• 负责人: KOTTAYIL I VARUGHESE
• 金额: $ 0.46万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954415
• 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; structural biology; synchrotron radiation; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 （i）Von Willebrand因子（VWF）的A1结构域与血小板受体受体糖蛋白（GP）iBalpha之间的相互作用在流血迅速的出血中起着至关重要的作用，其中血液流量很快，并且在病理血栓形成中也导致动脉闭塞。另外，GP ibalpha与凝血酶相互作用，凝血酶反过来激活血小板并调节血液凝结。这两种相互作用均通过糖蛋白（GP Ibalphan）的N末端结构域进行介导。该提案的目的是研究GPIBALPHAN与凝血酶和VWF A1的相互作用，以及通过晶体学技术的相互作用。 VWF A1和GPIBALPHAN中的突变会引起出血性疾病。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）细菌使用两个组件系统适应环境条件的变化。为了响应生长的恶化，某些类型的细菌形成孢子，以保留遗传物质，直到生长条件再次变得有利。枯草芽孢杆菌中孢子的形成受到称为磷酸层的两个组件系统的扩展版本。我们正在进行旨在阐明分子水平磷光信号传导机制的晶体学研究。