STRUCTURE AND ASSEMBLY OF HELICAL PLANT VIRUSES

这个提议的直接目标是描述粒子的 烟草花叶病毒（TMV）和其他螺旋病毒，包括烟草 Rattle病毒（TRV），分子细节。 这是一个更广泛的 目的：研究大分子的组装过程，特别是， 包括蛋白质和核酸在内的大分子结构的组装 acids. 亚细胞结构的组装是细胞生物学的主要步骤之一 在生长和分化中，组装的控制因此是一个主要的 监管机制 烟草花叶病毒是这类病毒的理想系统 研究，因为它的生物学和物理化学已经广泛 研究，它提供了机会，有关其机制， 组装，特别是控制该组装到其分子上， 结构 X射线衍射提供了一种极好的方法， 病毒的图像，足够详细地描述分子结构 和互动。 从TMV的3.6埃分辨率地图构建的模型将是 精制，并且分辨率至少扩展到3.0埃。 结构 将确定几种TMV菌株，包括U2菌株（用于 目前已有初步结果）。 结构的 TMV蛋白螺旋聚集体和TMV的先导衍生物也将 进一步研究。 所有这些系统都被选中，因为它们 重要的是在研究的羧基，形成控制网站， TMV的组装。 模型将与其他结构进行比较， 聚集体，主要是病毒的“盘”前体， 将不同状态之间转换的分子细节可视化 蛋白质的聚集。 同样的方法也适用于TRV，它与TMV有很大的不同 总结构。 低分辨率地图（CA。6埃）旨在 最初，但最终我们希望确定这种结构， 详细信息TMV 由于TMV是唯一的蛋白质-核酸相互作用 到目前为止已经详细描述了分子，重要的是 研究另一个系统，以建立我们的通用性或其他 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.