REGULATION OF CELL DIVISION

这项研究的长期目标是确定 参与细菌细胞分裂的分子机制和潜在的 时空调控机制。我们的工作重点是 FtsZ蛋白组装成一个细胞骨架环， 蛋白质的分裂位点和指导细胞分裂的细菌。最近 研究表明，FtsZ是一个结构和功能的同源物， 真核细胞骨架蛋白微管蛋白。像微管蛋白FtsZ经历动态 由GTP水解调节的组装。此外，FtsZ是几个目标， 调节细菌细胞分裂的抑制剂。最近的研究表明， 苏拉和MinC是FtsZ组装的抑制剂。苏拉被诱导以响应 DNA损伤和MinC是分裂位点选择系统的一部分。在 本建议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。据信，目前， 螯合FtsZ单体和MinC被认为使FtsZ聚合物不稳定。我们 目前的研究应进一步确定FtsZ和这些之间的相互作用， 抑制剂来测试假设的机制。此外，MinC的几个方面 将研究其作用方式，包括与MinD的相互作用， MinE，这导致它在细胞的两极之间振荡。此外，本发明还提供了一种方法， 研究不同的突变FtsZ应该揭示FtsZ的其他方面， 组装件.本提案还将审查FtsZ与 ZipA和FtsA。遗传学和生物化学实验被提议用于 研究这些蛋白质之间的相互作用表面以及 这些蛋白质在FtsZ组装中。分离出来的FtsZ突变体 作为体外实验的对照。另外的ftsZ（Ts）突变将是 分离并用于寻找抑制因子， 调节FtsZ组装的基因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 与微管蛋白相似，但也非常不同。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.