STRUCTURE OF AN AMINO ACID-SENSING RIBOSWITCH

氨基酸感应核开关的结构

• 批准号: 7955160
• 负责人: DINSHAW J PATEL
• 金额: $ 0.73万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955160
• 关键词: Amino Acids; Binding; Coenzymes; Computer Retrieval of Information on Scientific Projects Database; Drug Delivery Systems; Elements; Eukaryota; Evaluation; Funding; Gene Expression; Grant; Institution; Length; Lysine; Messenger RNA; Molecular; Molecular Conformation; Peptides; Prokaryotic Cells; Proteins; RNA; RNA-Binding Proteins; Research; Research Personnel; Resources; Signal Transduction; Source; Structure; United States National Institutes of Health; antimicrobial drug; attenuation; conformational conversion; improved; novel; stem; structural biology; sugar; three dimensional structure

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. Recent studies have shown that gene expression in both prokaryotes and eukaryotes can be controlled through interactions of mRNA elements, called riboswitches, with small cellular metabolites, such as coenzymes, sugars, amino acids and nucleobases. Riboswitches are typically composed of two regions. The first region forms evolutionary conserved and independently folded metabolite-binding domain, specific for a certain metabolite. The second region, non-conserved expression platform, carries gene expression signals. The conformational transitions associated with metabolite binding are interpreted through the expression platforms which regulate gene expression by typically translational or transcriptional attenuation. Our research efforts are focused on the determination of the three-dimensional structures of the riboswitch metabolite-sensing modules in the free and bound states, towards an improved understanding of the conformational transitions harnessed by the expression platforms for allosteric modulation of gene expression. These studies will uncover the molecular mechanisms dictating riboswitch function and will help in the evaluation of riboswitches as novel antimicrobial drug targets. Among several riboswitch classes, amino acid specific riboswitches have not been structurally characterized. Despite the fact that many amino acids can be specifically recognized by RNA on the RNA-protein interfaces, these riboswitches should adapt conformations different from the protein-binding RNA structures, because riboswitches can distinguish a single amino acid among many other natural amino acids, their precursors, and amino acids in the peptide context. The riboswitch specific to amino acid lysine (174-nt in length) is also distinct from earlier riboswitches (app. 70-nt in length), given its much larger size and multi-stem junctional secondary fold.

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代表。列出的机构是 对于中心，这不一定是调查员的机构。 最近的研究表明，原核生物和真核生物中的基因表达都可以通过mRNA元素的相互作用（称为核糖开关）与小细胞代谢物（例如辅酶，糖，糖，氨基酸和核试剂酶）来控制。核糖开关通常由两个区域组成。第一个区域构成了进化保守和独立折叠的代谢物结合结构域，该结构域特有特定于某种代谢物。第二个区域是未经保密的表达平台，带有基因表达信号。与代谢产物结合相关的构象转变通过表达平台来解释，这些平台通常通过翻译或转录衰减来调节基因表达。 我们的研究工作集中在自由和绑定状态中核糖开关代谢物传感模块的三维结构上，以提高对根据基因表达的变构调节的表达平台所利用的构象转变的理解。这些研究将揭示决定核糖开关功能的分子机制，并有助于评估核糖开关作为新型抗菌药物靶标。 在几种核糖开关类别中，氨基酸特异性核糖开关尚未在结构上表征。尽管RNA可以在RNA-蛋白界面上特异性地识别许多氨基酸，但这些核糖开关应适应与蛋白质结合RNA结构不同的构象，因为核糖开关可以区分许多其他天然氨基酸的单个氨基酸，它们的前体，其前体和氨基酸在肽座环境中。鉴于其尺寸更大和多型连接二级折叠，氨基酸赖氨酸特异的核糖开关（长度为174-nt）也不同于早期的核糖开关（App。70-NT）。