STRUCTURE AND ASSEMBLY OF HELICAL PLANT VIRUSES

这项提议的直接目标是描述粒子 烟草花叶病毒(TMV)和包括烟草在内的其他螺旋病毒 Rattle病毒(TRV)，分子细节。这构成了更广泛的 目的：研究大分子组装过程，特别是大分子组装过程。 涉及蛋白质和核的大分子结构的组装 酸。亚细胞结构的组装是主要步骤之一 在生长和分化中，组装的控制因此是一个主要的 监管机制。烟草花叶病毒是这种病毒的理想系统。 研究，因为它的生物学和物理化学已经被广泛地 研究，并提供了机会来叙述其作用机制 组装体，特别是该组装体对其分子的控制 结构。X射线衍射提供了一种很好的方法来获得 足够详细的病毒图像来描述分子结构 和互动。 从TMV的3.6埃分辨率地图建立的模型将是 精致，分辨率至少扩展到3.0埃。的结构 将确定几个烟草花叶病毒株系，包括U2株系(用于 已有初步结果)。的结构 TMV蛋白的螺旋聚集体和TMV的先导衍生物也将 进一步研究。所有这些系统之所以被选中，是因为它们 研究形成对照部位的羧基的重要性 TMV的组装。这些模型将与其他结构进行比较 聚集体，主要是病毒的“磁盘”前体，以便 可视化不同状态之间切换的分子细节 蛋白质的聚集。 同样的方法将适用于TRV，它与TMV有很大的不同 在总体结构上。低分辨率地图(约6埃)的目标是 最初，但最终我们希望以可比的方式确定这种结构 详情请转到TMV。由于TMV是唯一的蛋白质-核酸相互作用 到目前为止一直在分子上详细描述的，重要的是 检查另一个系统，以确定我们的 调查结果。

The immediate objective of this proposal is to describe the particle of tobacco mosaic virus (TMV) and other helical viruses, including tobacco rattle virus (TRV), in molecular detail. This forms part of a broader objective: to study the process of macromolecular assembly; in particular, the assembly of macromolecular structures involving proteins and nucleic acids. Assembly of sub-cellular structures is one of the principal steps in growth and differentiation, and control of assembly is thus a major regulatory mechanism. Tobacco mosaic virus is the ideal system for such studies, since its biology and physical chemistry are already extensively studied, and it offers the opportunity of relating its mechanism of assembly, and in particular the control of that assembly to its molecular structure. X-ray diffraction provides an excellent method of obtaining an image of the virus in sufficient detail to describe the moleculr structure and interactions. The model built from the 3.6 angstroms resolution map of TMV will be refined, and resolution extended at least to 3.0 angstroms. Structures of several strains of TMV will be determined, including the U2 strain (for which preliminary results are already available). Structures of the helical aggregates of TMV protein and a lead derivative of TMV will also be studied further. All of these systems have been chosen because of their importance in studying the carboxyl groups which form the control site in the assembly of TMV. The models will be compared with structures of other aggregates, principally the "disk" precursor to the virus, in order to visualize the molecular details of switching between the different states of aggregation of protein. The same methods will be applied to TRV, which is quite different from TMV in gross structure. A low-resolution map (ca. 6 angstroms) is aimed at initially, but eventually we hope to determine this structure in comparable detail to TMV. Since TMV is the only protein-nucleic acid interaction which has been described in molecular detail until now, it is important to examine another system to establish the generality or otherwise of our findings.