CONFORMATIONAL DYNAMICS OF ICOSAHEDRAL VIRUSES PROBED BY SAXS

通过 SAXS 探测二十面体病毒的构象动力学

• 批准号: 7721816
• 负责人: John Emil Johnson
• 金额: $ 0.4万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721816
• 关键词: Address; Antiviral Agents; Bacteriophages; Capsid; Capsid Proteins; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA; Data; Equilibrium; Funding; Future; Goals; Grant; Head; Insect Viruses; Institution; Kinetics; Measures; Monitor; Nucleic Acids; Protein Subunits; RNA; Research; Research Personnel; Resolution; Resources; Signal Transduction; Solutions; Source; Time; United States National Institutes of Health; Virion; Virus; neutralizing antibody; receptor binding; reconstruction

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 protein capsids of many viruses respond dynamically to environmental signals such as DNA or RNA packaging, receptor binding, and changes in pH or ionic composition. As a result, they undergo conformational changes that involve the concerted reorganization of hundreds of protein subunits and nucleic acid. Small-angle x-ray scattering (SAXS) is ideally suited to monitoring these structural changes in solution. We propose to use SAXS to monitor the dynamic conformational changes observed in two types of icosahedral virus particles, 1) an empty phage head capsid composed of 420 identical subunits (HK97 bacteriophage) and 2) a ssRNA insect virus composed of 240 identical capsid proteins and encapsidated RNA (N-omega-V tetravirus). The data we obtain will be used for generating low-resolution 3D reconstructions as well as for quantitative analysis of time-resolved structural changes using Singular Value Decomposition (SVD). The primary intellectual goals of the proposed studies are to measure the extent of cooperativity among subunits during large-scale conformational changes of these massive and complex assemblies, and to probe for the existence of kinetic and equilibrium intermediate states. By quantitatively addressing these issues we hope to better understand virus function and to enlighten future strategies for targeting capsids with antiviral compounds and neutralizing antibodies.

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。 许多病毒的蛋白质衣壳对环境信号的动态反应，例如DNA或RNA包装，受体结合以及pH或离子组成的变化。 结果，它们发生了构象变化，涉及数百种蛋白质亚基和核酸的一致重组。 小角度X射线散射（SAX）非常适合监测溶液中的这些结构变化。 我们建议使用SAXS监测在两种类型的二十体病毒颗粒中观察到的动态构象变化，1）由420个相同亚基（HK97噬菌体）组成的空噬菌体头帽和2）由240个相同的帽蛋白和包容的RNA（N-ssrna）组成。 我们获得的数据将用于生成低分辨率3D重建以及使用单数值分解（SVD）的时间分辨结构变化的定量分析。 拟议的研究的主要智力目标是衡量这些大规模和复杂组件的大规模构象变化期间亚基之间的合作程度，并探究存在和平衡中间状态的存在。 通过定量解决这些问题，我们希望更好地了解病毒功能，并启动未来的策略，以靶向使用抗病毒化合物和中和抗体的衣壳。