SIGNAL TRANSDUCTION OF TWO-COMPONENT SYSTEM

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。 对于细菌来说，感知和适应环境变化和压力的能力对其持久性和生存至关重要。双组分系统(TCS)是细菌、真菌和一些植物通过调节基因表达来感知外部或内部信号并做出适当反应的一种基本机制。在许多病原微生物中，TCSs在致病和/或耐药中起着关键作用。一个典型的TCS由两个蛋白质组成：一个多结构域、多功能的传感器组氨酸激酶(HK)，用于监测环境信号；以及一个响应调节器(RR)，它通过磷酸转移反应接收来自传感器激酶的信号，并通过调节某些基因的表达来触发下游反应。TCS信号转导的分子机制仍然知之甚少。本研究以枯草芽孢杆菌YycFG为模型，研究高分辨率TCS信号转导的分子基础。YycFG是一种基本的TCS，对低G+C革兰氏阳性菌具有特异性，如葡萄球菌、链球菌和肠球菌，这些细菌是人类感染的主要病原体，并可导致肺炎、脑膜炎、心内膜炎和菌血症等疾病。其中一些病原体，如炭疽杆菌和肉毒梭菌，被归类为潜在的生物恐怖因子。我们试图：(I)定义YycF的三维结构，以及(Ii)研究YycG和YycF之间的分子相互作用，这是磷转移的关键。

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. For bacteria, the ability to sense and adapt to environmental change and stress is crucial to persistence and survival. Two-component system (TCS) is a fundamental mechanism utilized by bacteria as well as fungi and some plants to sense external or internal signals and make appropriate responses through regulation of gene expression. TCSs play pivotal roles in pathogenesis and/or antibiotic resistance in many pathogenic microorganisms. A paradigmatic TCS consists of two proteins: a multi-domain, multi-function sensor histidine kinase (HK) that monitors environmental signals, and a response regulator (RR) that receives the signal from the sensor kinase through phosphotransfer reactions and triggers downstream responses through, e.g., regulation of expression of certain genes. Molecular mechanisms underlying TCS signal transduction remain poorly understood. The proposed research is aimed at molecular basis of TCS signal transduction at high resolution, using the YycFG of Bacillus subtilis as a model. YycFG is an essential TCS and is specific to low G+C Gram-positive bacteria such as Staphylococcus, Streptococcus and Enterococcus, which are leading causative agents of human infections and cause diseases including pneumonia, meningitis, endocarditis and bacteremia. Some of these pathogens, such as Bacillus anthracis and Clostridium botulinum, are classified as potential bioterror agents. We seek to: (i) define the three-dimensional architecture of YycF, and (ii) investigate the molecular interactions between YycG and YycF that are critical for phosphotransfer.