INVESTIGATING THE PROPOSED 'SWITCHING' MECHANISM OF VARIOUS RIBOSWITCHES

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。 核糖开关是主要在细菌中发现的结构化信使核糖核酸元件。在识别特定的细胞代谢后，这些RNA直接负责在转录和翻译水平上调节基因的表达。由于核糖开关主要在细菌中发现，并代表着潜在的新药物靶点，这些RNA最近在结构-功能关系方面引起了人们的兴趣。代谢物诱导的构象变化是核糖开关功能机制的核心部分。 我们的研究集中在代谢物结合引起的结构变化的本质上。文献中的许多讨论都在争论配体识别是导致RNA的全球变化，还是仅仅导致结合口袋周围的局部重排。我们在BioCAT光束线上的研究表明，不同的核糖开关的行为是独特的，这可能表明构象变化是根据每个核糖开关的遗传背景进行调整的。 此外，我们在BioCAT的工作使我们能够直接观察识别第二信使环二鸟酸酯的核糖开关的代谢物结合和无代谢物构象。这是第一个报道的核糖开关，它识别第二信使，负责调节多种参与信号传递的基因，而不是更常见的核糖开关靶标。

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. Riboswitches are structured mRNA elements found predominantly in bacteria. Upon recognition of specific cellular metabolies these RNAs are directly responsible for regulating gene expression at both the transcriptional and translational levels. Because riboswitches are found predominantly in bacteria and represent potential novel drug targets, these RNAs have been of recent interest for structure-function relationships. A metabolite-induced conformational change is a central part of the proposed mechanism of riboswitch function. Our research has focused on the nature of the structural changes elicited by metabolite-binding. Much discussion in the literature has debated whether ligand recognition results in global changes in the RNA or simply local rearrangements around the binding pocket. Our research at the BioCAT beamline demonstrates that different riboswitches behave idiosyncratically, perhaps indicating that the conformational changes are tuned to the genetic context of each riboswitch. Additionally, our work at BioCAT has allowed direct observation of the metabolite-bound and metabolite-free conformation of a riboswitch that recognizes the second messenger cyclic diguanylate. This is the first riboswitch reported which recongizes a second messenger and is responsible for regulating a wide variety of genes involved in signaling instead of the more common riboswitch targets relating