SAXS STUDIES ON PROTEIN-NUCLEIC ACID COMPLEXES

蛋白质-核酸复合物的 SAXS 研究

• 批准号: 7954931
• 负责人: ANEEL K. AGGARWAL
• 金额: $ 0.65万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954931
• 关键词: Antiviral Agents; Biophysics; Cells; Chemicals; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA; Enzymes; Funding; Genes; Grant; Human; Human Virology; Immune; Immune response; Immunology; Institution; Interferon Type I; Invaded; Mechanics; Modeling; Molecular Conformation; Molecular Motors; Motor; Nucleic Acids; Polymerase; Production; Proteins; Research; Research Personnel; Resources; Role; Shapes; Signaling Protein; Source; Testing; Tretinoin; United States National Institutes of Health; Viral; Virus; Virus Diseases; Work; conformational conversion; fascinate; helicase; restriction enzyme; sensor

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 first project is to study the role of conformational transitions in the viral sensor protein RIG-I in viral infection. Many human cells are capable of sensing viral infection and mounting an innate immune response1. How this antiviral immune response is triggered has been a central question in the fields of virology and human immunology. The clearest answer to this puzzle has come recently with the discovery of retinoic acid inducible gene-I (RIG-I) like proteins as the primary sensors of invading viruses, leading to the production of type I interferons (IFN-¿/¿) and other antiviral proteins. An unresolved question is how RIG-I recognizes and responds to virus infection. The current model for RIG-I is that it exists in a "closed" conformation in uninfected cells, but upon viral infection and association with virus-specific RNAs (and ATP) it changes to an "open" conformation, allowing interaction with downstream signaling proteins. SAXS studie sare proposed to test this hypothetical model. The second project studies the ATP-dependent molecular motor: EcoP15I, a Type III restriction enzyme that moves on the DNA. Along with enzymes such as helicases and polymerases, they convert chemical energy into mechanical energy for work on the DNA. Although, type III restriction enzymes have been studied biochemically and genetically for >35 years, there is still no structural information on these fascinating ATP dependent motors. SAXS analysis of the complex will provide an independent assessment of its size and shape that may be compared to our preliminary EM analysis.

该副本是使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，这是调查员的机构。 第一个项目是研究构象转变在病毒传感器蛋白IRIG-I中在病毒感染中的作用。许多人类细胞能够感知病毒感染并安装先天免疫响应1。在病毒学和人类免疫学领域，如何触发这种抗病毒免疫响应是一个核心问题。最近，最明确的答案是在发现视黄酸诱导的基因-I（RIG-I）之类的蛋白（如蛋白）作为入侵病毒的主要传感器，从而导致I型干扰素（IFN-€/€）和其他抗病毒蛋白的产生。一个尚未解决的问题是IRIG-I如何认识并应对病毒感染。 RIG-1的当前模型是它存在于未感染的细胞中的“封闭”会议中，但是在病毒感染并与病毒特异性RNA（和ATP）相关联时，它会变为“开放”构象，从而使其与下游信号蛋白相互作用。 SAXS Studio Sare提议测试这一假设模型。第二个项目研究了依赖ATP的分子运动：ECOP15I，一种在DNA上移动的III型限制酶。它们与诸如解旋酶和聚合酶之类的酶一起将化学能转化为机械能以进行DNA的工作。尽管III型限制性酶已经在生化和一般地研究了35年，但仍然没有关于这些迷人的ATP依赖电机的结构信息。对该复合物的SAXS分析将提供对其大小和形状的独立评估，可以将其与我们的初步EM分析进行比较。