中文摘要
Z环是由细胞骨架蛋白FtsZ自组装形成的细菌细胞分裂中的一个关键细胞器。Z环定位在细胞中部,依次结合其他分裂蛋白,让一系列细胞分裂事件有序地发生。随隔膜形成,Z环将GTP水解的化学能转化为向内的机械力,缩小自身直径,拉动隔膜内陷,直至最终分裂细胞。我们的前期工作回答了FtsZ原丝纤维是如何将GTP水解的化学能转化为相邻亚基之间的构象变化,并进一步转化为一个改变细胞膜曲度的张力的。但仍有一些亟待解决的重要科学问题,如FtsZ原丝纤维如何进一步组装成Z环的?GTP水解而导致的FtsZ原丝纤维构象变化如何进一步动态地重组Z环,使之逐渐收缩?以及Z环收缩又是如何与细胞基本生理紧密结合,在细胞周期中被精密地调控?本项目围绕这些问题,采用多学科交叉手段,有机结合体内体外实验,从细胞生物学、结构生物学和生物物理化学多方面全面系统的研究Z环的结构、收缩和调控的分子机制。为靶向Z环的药物设计提供直接的信息。
英文摘要
Bacterial cytoskeletal protein FtsZ polymerizes into protofilaments. These protofilaments further organize into a structure termed the Z ring - a key cell division organelle. Z ring recruits the accessory division proteins to the septum in a sequential manner, localizing the highly orchestrated division events to specific sub-cellular compartments. With the formation of the septum, Z ring converts the chemical energy of GTP hydrolysis to a mechanical constrictive force, reduces its diameter, until finally divides a cell. We have addressed how FtsZ protofilament converts the chemical energy of GTP hydrolysis to a conformational change between two FtsZ subunits in a protofilament, and how the straight-to-curved transition exerts constrictive forces on the envelope. However, some important scientific questions remain to be addressed. For example, how FtsZ protofilaments further organize to form a Z ring? How Z ring remodels itself to contract? How Z ring contraction is regulated by cell physiology? Focusing on these topics, we propose to combine in vivo and in vitro studies, systematically study the molecular mechanism of Z ring structure, contraction and regulation, using interdisciplinary approaches of cell biology, structural biology, biophysics and biochemistry. This project will provide direct structural and molecular information for drug design targeting Z ring.
