Packaging and Structure of Viral Genomes

描述（由申请人提供）：病毒生命周期的关键步骤之一是基因组的包装。这项研究的目的是了解结构，动力学和热力学方面的病毒包装在两个简单的，但非常不同的系统。Lambdoid噬菌体使用atp驱动的马达将双链DNA （ds-DNA）基因组插入预先形成的衣壳中。诺达病毒通过一系列精心安排的蛋白质- rna和蛋白质-蛋白质结合事件，在含有两条单链rna的基因组周围组装蛋白质衣壳。我们将使用各种工具开发一系列越来越详细的噬菌体P4三维分子模型；两种RNA病毒，卫星烟草花叶病毒（STMV）和pariacoto病毒（PaV）。PaV是noddaviridae家族的一个很有特征的成员。这项研究的目的是使各种各样的实验数据合理化，并提出假设，以激励未来的实验工作。对ds-DNA噬菌体的研究部分是基于这样的假设，即该系统是开发更精确处理静电效应的工具的理想选择，这对于我们进一步了解核酸的结构和热力学问题至关重要。对STMV和PaV的研究将验证这样一个假设，即包装中的RNA选择不是由对特定RNA序列或小的局部结构基序的识别驱动的，而是由病毒RNA采用二级结构的能力驱动的，二级结构与病毒对称性施加的限制相兼容。

DESCRIPTION (provided by applicant): One of the critical steps in the life cycle of a virus is the packaging of the genome. This research is aimed at understanding the structural, kinetic and thermodynamic aspects of viral packaging in two simple, but very different, systems. Lambdoid bacteriophage use an ATP-driven motor to insert a double-stranded DNA (ds-DNA) genome into a preformed capsid. Nodaviruses assemble the protein capsid around a genome containing two single-stranded RNAs through an orchestrated series of protein-RNA and protein-protein binding events. We will use a variety of tools to develop a series of increasingly detailed three-dimensional molecular models for bacteriophage P4; and for two RNA viruses, satellite tobacco mosaic virus (STMV) and pariacoto virus (PaV). PaV is a well-characterized member of the Nodaviridae family. This research is aimed at rationalizing a wide variety of experimental data, and at developing hypotheses that will motivate future experimental work. The work on ds-DNA bacteriophage is motivated, in part, by the hypothesis that this system is ideal for the development of tools for the more accurate treatment of electrostatic effects, which is critical for further advances in our understanding of structural and thermodynamic issues in nucleic acids. The work on STMV and PaV will test the hypothesis that RNA selection in packaging is not driven by the recognition of a particular RNA sequence or small local structural motif, but by the viral RNA's ability to adopt secondary structures compatible with constraints imposed by viral symmetry.