REGULATION OF CELL DIVISION

这项研究的长期目标是确定 细菌细胞分裂的分子机制及其基础 空间和时间调控机制。我们的努力集中在 FtsZ蛋白，组装成一个细胞骨架环，招募另一个 蛋白质到分裂部位，并指导细菌中的细胞分裂。近期 研究表明，FtsZ是结构和功能上的同源物。 真核细胞骨架蛋白微管蛋白。像微管蛋白一样，FtsZ经历了动态变化 由GTP水解酶调节的组装。此外，FtsZ也是几个 调节细菌细胞分裂的抑制剂。最近的研究表明， Sula和Minc是FtsZ组装的抑制剂。秀拉是为了回应 DNA损伤和Minc是组织选址系统的一部分。在 目前的生物化学和遗传学研究旨在确定 这些抑制剂的作用机制。目前，人们认为秀拉 封闭剂FtsZ单体和Minc被认为会破坏FtsZ聚合物的稳定性。我们的 目前的研究应该进一步定义FtsZ和这些基因之间的相互作用 抑制剂，以测试假设的机制。此外，Minc的几个方面 将调查行动模式，包括其与思维的互动和 我的，这会导致它在细胞的两极之间振荡。此外, 研究各种突变的FtsZ应该会揭示FtsZ的其他方面 集合。本提案还将审查FtsZ之间的互动 以及ZipA和FTSA。基因和生化实验被提议用来 研究这些蛋白质之间的相互作用面及其作用 这些蛋白质在FtsZ组装中。将被分离的FtsZ突变体将服务于 作为体外实验的对照。其他FtsZ(Ts)突变将是 分离并用来寻找抑制子，试图找到其他蛋白质 来规范FtsZ组装。过去几年的研究表明， FtsZ是细菌细胞分裂的普遍特征。它有很大的相似性 对微管蛋白，但也是相当独特的。因此，它应该被证明是一个 用于抗菌治疗的有用的新靶点。

The long-term objectives of this research are to determine the molecular mechanisms involved in bacterial cell division and the underlying spatial and temporal regulatory mechanisms. Our efforts have focused on the FtsZ protein which assembles into a cytoskeletal ring that recruits other proteins to the division site and directs cell division in bacteria. Recent work has shown that FtsZ is a structural and functional homologue of the eukaryotic cytoskeletal protein tubulin. Like tubulin FtsZ undergoes dynamic assembly that is regulated by GTP hydrolysis. Also, FtsZ is a target of several inhibitors that regulate cell division in bacteria. Recent work has shown that SulA and MinC are inhibitors of FtsZ assembly. SulA is induced in response to DNA damage and MinC is part of the division site selection system. In the present proposal biochemical and genetic studies are designed to determine the mechanism of action of these inhibitors. At present SulA is thought to sequester FtsZ monomers and MinC is thought to destabilize FtsZ polymers. Our present studies should further define the interaction between FtsZ and these inhibitors to test the postulated mechanisms. Also, several aspects of MinC's mode of action will be investigated including its interaction with MinD and MinE, which cause it to oscillate between the poles of the cell. In addition, studying the various mutant FtsZs should reveal additional aspects of FtsZ assembly. The present proposal will also examine the interaction between FtsZ and ZipA and FtsA. Genetic and biochemical experiments are proposed to investigate the interacting surfaces between these proteins and the role of these proteins in FtsZ assembly. FtsZ mutants that will be isolated will serve as controls for in vitro experiments. Additional ftsZ(Ts) mutations will be isolated and used to look for suppressors in an attempt to find other proteins that regulate FtsZ assembly. Research over the past few years has shown that FtsZ is a universal feature of bacterial cell division. It has great similarity to tubulin but is also quite distinct. As a result it should prove to be a useful, novel target for antimicrobial therapy.