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

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。 (I)血管性血友病因子(VWF)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迅速时止血以及导致动脉闭塞的病理性血栓形成中起关键作用。此外，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固。这两种相互作用都是通过糖蛋白的N-末端结构域(GP IbalphaN)来调节的。这项建议的目的是用结晶学技术研究GPIbalphaN与凝血酶、vWF A1和凝血酶的相互作用。VWF A1和GPIbalphaN的突变会导致出血性疾病。我们正在通过分析络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)细菌使用双组分系统来适应环境条件的变化。为了应对不断恶化的生长条件，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一种名为磷继电器的双组分系统的扩展版本控制的。我们正在进行结晶学研究，目的是在分子水平上阐明磷光传递信号的机制。

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.