Structural study of transmembrane interactions in the bacterial divisome

描述（由申请人提供）：细胞分裂是细菌生命中最基本和最具挑战性的过程之一。分裂体是主要由膜蛋白组成的复合物，其在细胞中期组装并且是细菌细胞分裂发生所必需的。分裂体的结构构造，特别是其跨膜区的组织，仍然是个谜。解开这个组织是一个重要的目标，充分了解的机制，参与细菌分裂及其调控。该提案的目标是对分裂体组装的核心的六个单跨膜蛋白（ZipA，FtsL，FtsB，FtsQ，FtsI和FtsN）进行结构和功能分析。所提出的方法是多学科的，具有体外相互作用的生物物理表征，诱变，计算建模和X射线晶体学来研究它们的膜外结构域。我们的主要目标是确定跨膜区的6个divisomal蛋白相互作用的能力，测量其协会的能量，并确定其结构组织。这个项目解决了一个关键的障碍 在理解细菌细胞分裂方面取得了进展，即缺乏关于分裂体膜区域结构组织的信息。通过开始解开复杂的结构和机制细节，该项目将为开发理解和控制细菌生长的新策略奠定重要的基础。

DESCRIPTION (provided by applicant): Cell division is one of the most fundamental and challenging processes in the life of bacteria. The divisome is a complex composed primarily of membrane proteins that assembles at mid-cell and is necessary for bacterial cell division to occur. The structural architecture of the divisome, and the organization of its transmembrane region in particular, are still mysterious. Unraveling this organization is a crucial goal for a ful understanding of the mechanisms that are involved in bacterial division and its regulation. This goal of this proposal is a structural and functional analysis of six single-span transmembrane proteins (ZipA, FtsL, FtsB, FtsQ, FtsI and FtsN) that are central to the assembly of the divisome. The proposed approach is multi-disciplinary, with a biophysical characterization of the interactions in vitro, mutagenesis, computational modeling and X-ray crystallography to study their extra-membranous domains. Our main objectives are to determine the ability of the transmembrane region of the six divisomal proteins to interact; measure the energetics of their association; and determine their structural organization. This project addresses a critical barrier to progress in understanding bacterial cell division, namely the lack of information on the structural organization of the membrane region of the divisiome. By beginning to unravel the structural and mechanistic details of the complex, this project will establish important groundwork needed for the development of new strategies for understanding and controlling bacterial growth.