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进行的。可分为 那些看起来绝对必要并开展核心活动的组织，以及那些看起来是 并且可以通过核心中的过表达或突变来绕过 成分E.大肠杆菌中包含微管蛋白同源物FtsZ，其组装成 通过FtsA连接到膜上的纤维。FtsA作为一个枢纽，招募酶， FtsW/FtsI，需要制造隔PG。此外，除了这些核心蛋白，非核心蛋白包括 FtsE/FtsX调节分裂体组装，并将间隔PG合成与PG水解偶联，ZipA和 FtsZ、在募集和DNA分离中起作用的FtsK和FtsN的额外膜系链 从而引发分隔FtsQ/FtsL/FtsB是高度保守的，形成一个参与分裂的复合体， 组装和调节。它们也可能是核心机器的一部分。在本提案中，我们将测试我们的 FtsZ协同组装模型，进一步利用FtsE/FtsX进一步深入了解其在分裂中的作用 组装和调节。我们还将利用重要细胞基因的显性负突变 通过一种新的筛选方法分离出来，以了解蛋白质构象的变化， 调节分裂体的蛋白质相互作用。我们还将利用从研究细胞中获得的知识， 求一个最小的整除。

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.