Regulation and Mechanism of the C. Crescentus Cytokinetic Ring

 描述(由申请人提供)：为了产生可存活的后代，需要忠实地执行细胞质分裂。在细菌中，胞质分裂是由细胞骨架GTP酶FtsZ调控的。FtsZ聚合形成细胞动力学Z-环，指导二十多个其他因子的组装。总之，分裂机制促进了膜的收缩和分裂，以及肽聚糖(PG)细胞壁的重塑，最终将细胞一分为二。尽管FtsZ在大多数细菌中具有保守和必要的功能，但它在细胞质分裂中的确切作用仍不清楚。除了作为支架的作用外，FtsZ还被假设为产生收缩力量和/或调节PG重构。它是否以及如何在细胞中履行这些功能是未知的。与其他细胞骨架蛋白一样，FtsZ的组装特性和结构是定义和执行其功能的核心。利用基因， 通过细胞生物学、生化和先进的成像方法，这项建议解决了FtsZ聚合物和Z-环组装的三种不同调控模式如何在模式细菌新月弯杆菌中以确定的方式改变其功能输出。目的1研究FtsZ聚合物如何被不同的拴系蛋白物理定位于内膜，从而将FtsZ的活性导向不同的功能。目的2重点研究FtsZ原丝曲率如何促进包膜收缩。目的3确定无序的FtsZ的C-末端连接子如何以调节PG重塑酶所需的方式影响其组装和结构。这项拟议中的研究的成功完成将使人们对细菌王国中FtsZ功能的机制有更广泛的了解。鉴于FtsZ在细菌中的重要性，了解它指导生长和分裂的机制将有助于它成为新型抗生素的靶标。

 DESCRIPTION (provided by applicant): The faithful execution of cytokinesis is required to produce viable offspring. In bacteria, cytokinesis is orchestrated by the cytoskeletal GTPase, FtsZ. FtsZ polymerizes to form a cytokinetic Z-ring that directs assembly of more than two dozen other factors. Together, the division machinery promotes constriction and fission of the membranes and remodeling of the peptidoglycan (PG) cell wall to ultimately split the cell into two. Despite its conserved and essential function in the majority of bacteria, the precise role of FtsZ in cytokinesis remains poorly defined. In addition to acting as a scaffold, FtsZ is hypothesized to generate constrictive force and/or to regulate PG remodeling. If and how it fulfills these functions in the cell is unknown. Like other cytoskeletal proteins, the assembly properties and structure of FtsZ are central to defining and executing its function. Using genetic, cell biological, biochemical, and advanced imaging approaches, this proposal addresses how three distinct modes of regulating of FtsZ polymer and Z-ring assembly alter its functional output in defined ways in the model bacterium Caulobacter crescentus. Aim 1 addresses how FtsZ polymers are physically targeted to the inner membrane by different tethering proteins to direct FtsZ activity to different functions. Aim 2 focuses on how FtsZ protofilament curvature is used to promote envelope constriction. Aim 3 determines how the disordered C-terminal linker of FtsZ affects its assembly and structure in a manner required for the regulation of PG remodeling enzymes. Successful completion of the proposed research will yield broad insights into the mechanisms of FtsZ function across the bacterial kingdom. Given the essentiality of FtsZ in bacteria, understanding the mechanisms by which it directs growth and division will facilitate its development as a target for novel antibiotics.