SEQUENCE ANALYSIS OF THE BACTERIAL FLAGELLAR MOTOR

这项建议旨在理解几个基本的 生物过程--能量传递、二元转换和细胞器 装配--以沙门氏菌的细菌鞭毛为例 鼠伤寒杆菌。虽然该提案是基础研究之一，但知识 Gain被其他正在研究细菌作用的人使用 鞭毛和运动性在发病机制中的作用。 提案的第一部分涉及到 鞭毛马达称之为开关。交换机需要用于 鞭毛旋转并控制其旋转方向 (逆时针与顺时针)的行为称为趋化性。它 至少由三种不同的蛋白质组成。这些基因的突变 蛋白质，取决于它们的严重程度，可以导致 鞭毛切换，旋转，甚至组装。建议数 研究将建立在现有的氨基酸变化知识的基础上 对这些缺陷负责，这些缺陷是从一个大型的 自发突变体，并利用这些知识作为探索的基础 更详细地说，通过系统的删除和站点定向的点 突变，开关功能的各个方面。 建议的第二部分涉及以下主要结构要素： 鞭毛，包括它的螺旋桨，以及它们是如何 被识别为有别于其他细胞成分，以便 有选择地出口。这些蛋白质形成了一个家族，其主要的 结构是已知的。它们有几个共同的特点，包括周期性 疏水残基和局部共有序列的重复。这些 功能将以选择性的方式发生变化，其后果是 对出口和组装进行监控，试图了解认识 进程。

This proposal is directed towards an understanding of several basic biological processes-energy transduction, binary switching, and organelle assembly-as exemplified in the bacterial flagellum of Salmonella typhimurium. While the proposal is one of basic research, the knowledge gained is used by others who are studying the role of bacterial flagellation and motility in pathogenesis. The first part of the proposal involves an important element of the flagellar motor called the switch. The switch is needed for the flagellum to rotate and for it to control its direction of rotation (counterclockwise vs clockwise) in the behavior called chemotaxis. It is made up from at least three different proteins. Mutations in these proteins, depending on how severe they are, can cause failure of the flagellum to switch, to rotate, or even to assemble. The proposed research will build on existing knowledge of the amino acid changes responsible for these defects, obtained from a large library of spontaneous mutants, and use this knowledge as the basis for exploring in more detail, by systematic deletions and site-directed point mutations, the various aspects of switch function. The second part of the proposal involves the main structural elements of the flagellum, including its helical propeller, and how they are recognized as being distinct from other cellular components in order to be selectively exported. These proteins form a family, whose primary structures are known. They share several features, including periodic repeats of hydrophobic residues and local consensus sequences. These features will be mutated in a selective fashion, and the consequences for export and assembly monitored in an attempt to understand the recognition process.