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。分裂体是一种主要由膜蛋白组成的复合体，它聚集在细胞中间，是细菌细胞分裂发生所必需的。分裂体的结构结构，特别是其跨膜区域的组织结构，仍然是一个谜。解开这个组织是充分理解细菌分裂及其调控机制的关键目标。本提案的目标是对六种单跨膜蛋白（ZipA, FtsL, FtsB, FtsQ， FtsI和FtsN）的结构和功能进行分析，这些蛋白是分裂体组装的核心。所提出的方法是多学科的，包括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六种分裂蛋白的跨膜区域相互作用的能力；测量它们结合的能量学；确定它们的结构组织。这个项目解决了一个关键的障碍

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.