INVESTIGATING THE PROPOSED 'SWITCHING' MECHANISM OF VARIOUS RIBOSWITCHES

研究各种核开关的拟议“转换”机制

• 批准号: 8168631
• 负责人: Nathan Baird
• 金额: $ 1.44万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168631
• 关键词: Bacteria; Binding; Computer Retrieval of Information on Scientific Projects Database; DNA Sequence Rearrangement; Drug Delivery Systems; Elements; Funding; Gene Expression; Genes; Genetic; Global Change; Grant; Institution; Ligands; Literature; Messenger RNA; Molecular Conformation; Nature; RNA; Reporting; Research; Research Personnel; Resources; Second Messenger Systems; Signal Transduction; Source; Structure; Structure-Activity Relationship; United States National Institutes of Health; Work; beamline; interest; novel; second messenger

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

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表示。列出的机构是 对于中心，这不一定是调查员的机构。 核糖开关是在细菌中主要发现的结构化mRNA元素。 一旦识别特定的细胞代谢，这些RNA直接负责调节转录和翻译水平的基因表达。 由于核糖开关主要在细菌中发现并代表了潜在的新药物靶标，因此这些RNA最近对结构功能关系具有最近的兴趣。 代谢物诱导的构象变化是提出的核糖开关功能机理的核心部分。 我们的研究集中在代谢物结合引起的结构变化的性质上。 文献中的许多讨论都辩论了配体识别是导致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，不同的核糖开关表现出色，也许表明构象变化已调整为每个核糖开关的遗传环境。 此外，我们在BioCat的工作允许直接观察核糖开关的代谢产物结合和无代谢物的构象，该核糖开关识别了第二个Messenger循环二甘氨酸酯。 这是第一个报道的核糖开关，它重新调节了第二个使者，并负责调节与信号传导有关的各种基因，而不是相关的更常见的核糖开关目标