REGULATION OF CELL DIVISION

这项研究的长期目标是确定细菌感染的分子机制。 细胞分裂和潜在的空间和时间调节机制。我们的工作重点是 FtsZ蛋白组装成细胞骨架环，将其他蛋白质募集到分裂位点， 指导细菌的细胞分裂。最近的研究表明，FtsZ是一种结构和功能同源物， 真核细胞骨架蛋白微管蛋白。与微管蛋白一样，FtsZ也经历动态组装， GTP水解。此外，FtsZ是调节细菌细胞分裂的几种抑制剂的靶标。 我们最近的工作表明，苏拉和MinC是FtsZ组装的抑制剂。苏拉被诱导， 对DNAdamage和MinC的响应是分部选址系统的一部分。在本提案中， 生物化学和遗传学研究旨在确定这些抑制剂的作用机制。在 本发明的苏拉被认为螯合FtsZ单体，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和这些抑制剂之间的相互作用，以测试假设的 机制等此外，将研究MinC作用模式的几个方面，包括它与 MinD和MinE，这导致它在细胞的两极之间振荡。此外，研究各种 突变的FtsZ应该揭示FtsZ组装的其他方面。 本提案还将审查FtsZ与ZipA和FtsA之间的互动。遗传和 提出了生物化学实验来研究这些蛋白质和蛋白质之间的相互作用表面。 这些蛋白在FtsZ组装中的作用。将分离的FtsZ突变体将用作体外试验的对照。 实验另外的ftsZ（Ts）突变将被分离并用于寻找抑制因子，以尝试 寻找其他调节FtsZ组装的蛋白质。 过去几年的研究表明，FtsZ是细菌细胞分裂的普遍特征。它有 与微管蛋白非常相似，但也非常不同。因此，它应该被证明是一个有用的，新的目标， 抗菌治疗

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 GTPhydrolysis. Also, FtsZ is a target of several inhibitors that regulate cell division in bacteria. Our recent work has shown that SulA and MinC are inhibitors of FtsZ assembly. SulA is induced in response to DNAdamage 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 it's 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 fewyears 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.