RAP PHOSPHATASES

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。 群体感应是细菌细胞间的通信过程，允许细菌群体一致行动，同步重要的表型变化。一类分泌的群体感应信号，称为Phr五肽，被输入细胞，在那里它们抑制称为RAPs的蛋白质的活性。为了确定Rap蛋白是如何发挥作用的，以及Rap功能是如何受到Phr肽的调节的，我们正在研究枯草杆菌Rap蛋白的两个亚集。一个Rap蛋白亚群通过去磷酸化产孢子信号转导途径中的一个中心蛋白来负向调节枯草杆菌产孢量，另一个Rap蛋白亚群通过阻止早期感受基因表达的主转录调节因子与靶DNA启动子结合来下调遗传能力的发展。我们已经结晶了Rap蛋白与他们的目标效应蛋白以及他们的调节Phr多肽的复合体。这些复合体的X射线晶体结构，结合生化和遗传学研究，将首次揭示Rap蛋白是如何发挥作用的，以及Phr肽是如何调节Rap蛋白活性的。

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. Quorum sensing is a bacterial cell-cell communication process that allows groups of bacteria to act in unison, synchronizing important phenotypic changes. One family of secreted quorum-sensing signals, called Phr pentapeptides, is imported into the cell where they inhibit the activity of proteins called Raps. To determine how Rap proteins function mechanistically, and how Rap functions are in turn regulated by Phr peptides, we are studying two subsets of Bacillus subtilis Rap proteins. One Rap protein subset negatively regulates sporulation in B. subtilis by dephosphorylating a central protein in the sporulation signal transduction pathway, the other subset of Rap proteins downregulates the development of genetic competence by preventing the master transcriptional regulator of early competence gene expression from binding to target DNA promoters. We have crystallized Rap proteins in complex with their target effector proteins, as well as with their regulatory Phr peptides. The X-ray crystal structures of these complexes, combined with biochemical and genetic studies, will reveal for the first time how Rap proteins function mechanistically and how Phr peptides regulate Rap protein activity.