FtsZ原丝纤维动态和结构变化在细菌分裂中的作用机制

细菌收缩环由十几种蛋白组成，是细菌完成分裂的重要结构。细菌骨架蛋白FtsZ是其中最主要的组成蛋白。FtsZ自聚合形成的高动态原丝纤维，在体内组装成高动态的细菌收缩环。在过去研究中，我们发现大肠杆菌FtsZ原丝纤维具有两个重要的特性：高动态性和与GTP水解偶合的从直形到弯形转变的特性。为进一步阐明收缩环的收缩机理，本项目主要从两方面进行研究：1.研究FtsZ这两种特性是否具有普遍性，是否有调控蛋白参与这些变化；2.进一步研究FtsZ-ZipA形成的高度弯曲原丝纤维的精细结构，探讨收缩力产生是否与FtsZ原丝纤维的从直形到弯性的转换有关。本项目将采用多种技术，将溶液中的动力学研究、脂质体中细菌收缩环的体外模拟研究和细菌体内收缩环的功能研究有机地结合起来,进一步阐明细菌的分裂机理。.对细菌分裂机理的阐明，不但具有重要的科学意义，而且可以为新型抗生素的筛选提供新思路新方法，具有重要的实践意义。

The central objective of this project is to elucidate the mechanisms of the force generated by the bacterial Z-ring（the contractile ring） and the roles of the highly dynamic FtsZ filaments. Bacterial cytoskeleton protein FtsZ, assembling into the Z-ring in vivo, is the key protein in bacterial cell division. However, since there is no motor protein, how the Z-ring generates the force is still poorly understood..In our previous studies, two FtsZ filaments conformations: straight conformation and highly curved conformation were found in vitro using electron microscopy. It is still controversial whether the transition between these two FtsZ conformations generates inward force and whether FtsZ highly dynamical properties are required for the Z-ring contraction. To address these questions, a series of FtsZs and FtsZ mutants from different species will be examined, and the relationship between the transition of two FtsZ filaments conformations and their dynamical properties will be studied using various biochemical and biophysical techniques, especially fluorescence techniques and electron-microscopy techniques..Furthermore, the dynamic Z-ring like structures will be reconstituted in various liposomes to provide us convincing evidence whether these two conformations of FtsZ filaments are essential to the Z-ring formation and contraction. Also, the approaches in vivo will be established to study their functions and to further understand the Z-ring function concerning the highly dynamic FtsZ filaments..Upon accomplishing this project, we expect to answer the following challenging questions: whether the transition between the FtsZ straight filaments and curved filaments is necessary to the Z-ring force generation and whether the highly dynamic FtsZ filaments play an important role in the Z-ring contraction. We will establish the model to address the mechanisms of the force generation of bacterial Z-ring and fully understand the highly dynamic FtsZ filaments. These studies will provide us novel strategies to develop novel antibiotics that target the bacterial cell division proteins in the future.