结核分枝杆菌是人类的主要致病菌之一，随着结核分枝杆菌耐药株的出现以及免疫抑制剂的应用，现有的抗生素和疫苗已经不能有效地预防和控制结核病，因此开发新的抗生素和疫苗迫在眉睫。近年来在细菌中发现的第二信使c-di-GMP能够调控包括生物被膜形成、毒力、运动以及细胞分化等多种生理活动，因而其调控和信号转导途径成为研究的热点。结核分枝杆菌中c-di-GMP浓度由两个关键酶Rv1357c和Rv1354c控制，但分子机制不清。由于Rv1354c由三个相对构象柔性的结构域（GAF-GGDEF-EAL）组成，我们将整合蛋白质晶体学和X射线小角散射对其全长和各个结构域的结构和功能进行研究，以期阐明其调控c-di-GMP合成与降解的机理。该研究将有助于深入了解结核分枝杆菌的致病机理，为研究新型抗生素和疫苗提供理论指导。

Mycobacterium tuberculosis is one of the major human pathogens and leads to approximately 3 million deaths annually. Upon the abuse of the antibiotics and other drugs, M. tuberculosis showed resistance to penicillium,as well as the multi-resistance to other antibiotics. The current vaccines could not efficiently prevent the infection of M. tuberculosis. Thus it is urgent to develop new antibiotics and/or vaccines. Recent reseach showed that c-di-GMP is a diffusible molecule that functions as a second messenger in bacteria including M. tuberculosis. However, little is known on the physiological function of c-di-GMP in M. tuberculosis. We will focus on the structure and function of Rv1357c and Rv1354c by X-ray diffraction and small angle X-ray scattering. The structure and function of the key enzymes involved in biosysthesis and degradation of c-di-GMP will help us to elucidate the molecular mechanism of homeostais of intracellular c-di-GMP, and provide structural insights into the development of novel antibiotics and/or vaccines.