Packaging and Structure of Viral Genomes

描述(由申请人提供)：病毒生命周期中的关键步骤之一是基因组的包装。这项研究旨在了解病毒包装在两个简单但非常不同的系统中的结构、动力学和热力学方面。Lambdoid噬菌体使用ATP驱动的马达将双链DNA(ds-DNA)基因组插入到预先形成的衣壳中。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，将蛋白质衣壳组装在包含两个单链RNA的基因组周围。我们将使用各种工具为噬菌体P4以及卫星烟草花叶病毒(STMV)和副冠状病毒(PAV)这两种RNA病毒开发一系列日益详细的三维分子模型。PAV是Nodaviridae家族中一个很有特色的成员。这项研究的目的是使各种各样的实验数据合理化，并开发假说，以激励未来的实验工作。DS-DNA噬菌体的工作在一定程度上是由于这样一个假设，即该系统是开发更准确地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中的结构和热力学问题至关重要。STMV和PAV方面的工作将检验这一假设，即包装中的RNA选择不是由特定RNA序列或小的局部结构基序的识别驱动的，而是由病毒RNA采用与病毒对称性施加的限制相兼容的二级结构的能力驱动的。

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.