Regulation of Cell Division

摘要 大多数细菌的细胞分裂是由一组保守的必需蛋白质完成的。它们可以分为 那些看起来绝对必要并执行核心活动的，以及那些似乎已被添加的 为了调节的目的，可以通过核心的过度表达或突变而绕过 组件。大肠杆菌的核心成分包括微管蛋白同系物FtsZ，它组装成 被FTSA拴在膜上的细丝。FTSA是招募酶的枢纽， FtsW/FTSI，需要制作间隔PG。此外，除了这些核心蛋白外，非核心蛋白还包括 FTSE/FtsX，它调节分裂组组装，并将间隔PG的合成与PG的水解结合在一起，ZipA和 FtsZ、FtsK和FtsN的额外膜系绳，FtsK在招募和DNA分离中起作用 这会引发隔膜。FtsQ/FtsL/FTSB高度保守，形成一个参与分裂组的复合体 集结与规范。它们很可能也是核心机制的一部分。在这个提案中，我们将测试我们的 FtsZ的协同组装模型，进一步利用FTSE/FtsX进一步深入了解其在分裂组中的作用 集结与规范。我们还将利用基本细胞基因的显性负突变。 通过一种新的筛选分离出来，以了解导致蛋白质构象变化的蛋白质构象变化 调节分裂的蛋白质相互作用。我们还将利用从研究细胞中获得的知识 除法来构造一个最小除数。

Abstract Cell division in most bacteria is carried out by a conserved set of essential proteins. They can be divided into those that appear absolutely essential and carry out core activities and those that appear to have been added to the core for regulatory purposes and can be bypassed by overexpression of or mutation in a core component. The core components in E. coli include the tubulin homologue FtsZ which assembles into filaments that are tethered to the membrane by FtsA. FtsA serves as a hub that recruits the enzymes, FtsW/FtsI, needed to make septal PG. In addition, to these core proteins the noncore proteins include FtsE/FtsX which regulates divisome assembly and couples septal PG synthesis to PG hydrolysis, ZipA an additional membrane tether for FtsZ, FtsK which plays a role in recruitment and DNA segregation, and FtsN which triggers septation. FtsQ/FtsL/FtsB are highly conserved and form a complex involved in divisome assembly and regulation. They are likely part of the core machinery as well. In this proposal, we will test our model for cooperative assembly of FtsZ, further exploit FtsE/FtsX to gain further insight into its role in divisome assembly and regulation. We will also take advantage of dominant negative mutations in essential cell genes that were isolated by a novel screen to understand the changes in protein conformation that lead to changes in protein interactions that regulate the divisome. We will also use the knowledge gained from studying cell division to construct a minimal divisome.