STRUCTURAL ORIGINS OF NUCLEIC ACID SEQUENCE DISCRIMINATION BY PROTEINS

通过蛋白质区分核酸序列的结构起源

• 批准号: 7954344
• 负责人: JOHN J. PERONA
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954344
• 关键词: Base Sequence; Biological; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallization; Cysteine-tRNA ligase; DNA Restriction-Modification Enzymes; Discrimination; Enzymes; Funding; Gene Expression Regulation; Grant; Heart; Human; Hydrogenase; Institution; Isoenzymes; Methane; Nucleic Acids; Nucleic acid sequencing; Organism; Pathway interactions; Play; Production; Proteins; Research; Research Personnel; Resources; Role; Source; Structure; System; Transfer RNA; United States National Institutes of Health; mutant; novel; structural biology; synchrotron radiation

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. The ability of proteins to discriminate among nucleic acid sequences is at the heart of gene regulation and translational control in all organisms. Here we propose detailed x-ray crystallographic studies of protein-DNA and protein-RNA complexes of bacterial, human, and archaeal origins which elucidate this common theme in a variety of important biological contexts. Systems to be studied for which crystal structures of components to a larger assembly have been determined, or for which native enzymes/mutants have been solved are the transcriptional regulator Lrp, the glutaminyl and cysteinyl-tRNA synthetases (CysRS), and the DNA restriction-modification enzymes M.HhaI and EcoRV. Newer projects for which crystals are available, or for which protein-nucleic acid complexes are being screened for crystallization, are the human CysRS, two enzymes from a novel tRNA biosynthetic pathway in M. mazei, and tRNA complexes with isozymes of a hydrogenase from the methanogenesis pathway of M. jannaschii, which may play a role in regulating anaerobic methane production.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 蛋白质区分核酸序列的能力是所有生物体基因调控和翻译控制的核心。 在这里，我们提出对细菌、人类和古细菌起源的蛋白质-DNA 和蛋白质-RNA 复合物进行详细的 X 射线晶体学研究，阐明了各种重要生物学背景中的这一共同主题。 要研究的系统是转录调节因子 Lrp、谷氨酰胺酰和半胱氨酰-tRNA 合成酶 (CysRS) 以及 DNA 限制性酶，这些系统已确定较大组件的组件晶体结构，或者已解决了天然酶/突变体的问题。修饰酶 M.HhaI 和 EcoRV。 可用晶体或正在筛选蛋白质-核酸复合物结晶的新项目是人类 CysRS（来自 M. mazei 中新型 tRNA 生物合成途径的两种酶），以及与来自 M. mazei 的氢化酶同工酶的 tRNA 复合物。 M. jannaschii 的产甲烷途径，可能在调节厌氧甲烷产生中发挥作用。