大肠杆菌趋化性信号转导通路中甲基转移酶CheR与丝氨酸受体Tsr间的互作机制

趋化性是细菌感知胞外刺激、适应环境的重要行为，在多类生物进程中都发挥关键作用。大肠杆菌趋化性信号转导通路是细菌跨膜信号转导的典型研究模型，其甲基转移酶CheR能甲基化修饰受体，降低受体对刺激物的敏感性。近期研究发现CheR还具有效果相反于甲基化修饰受体的新功能，CheR通过与Tsr受体相互作用来增强受体对刺激物的敏感性。然而，CheR与Tsr受体间是如何通过相互作用影响受体甲基化修饰及信号转导状态等科学问题尚未解决。本项目将结合随机突变、化学交联、免疫印迹、荧光共振能量转移等遗传学、生理和生化的方法，定位CheR与Tsr受体间互作的关键位点，解析关键位点在CheR的两种功能及改变Tsr受体信号转导状态中的作用。本项目的完成将揭示CheR与Tsr受体间的互作机制，为大肠杆菌趋化性信号转导研究提供新的视角，对解析细菌趋化性和跨膜信号转导机制具有重要的科学意义。

Chemotaxis is the behavior that enables bacteria to sense the extracellular environment and adapt to the environment through transmembrane signal transduction. It plays a key role in many different types of biological processes. Escherichia coli chemotactic signal transduction pathway is the model system for studying transmembrane signal transduction. The methyl transferease CheR can modify receptor proteins by methylation, which results in reducing receptor sensitivity to stimuli. A recent study has found that CheR also has a new function opposite to the effect of methylation modification: CheR interacts with Tsr receptor to enhance the sensitivity of Tsr receptor to stimuli. Key scientific questions such as how CheR and Tsr receptor interact with each other to affect the methylation modification and signal transduction status of the receptor remain to be resolved. This project will combine genetic, physiological and biochemical methods such as random mutagenesis, cysteine cross-linking, immunoblotting, Förster Resonance Energy Transfer to identify key amino acid residues on CheR and Tsr receptor that are critical for the functional interaction, and analyze the roles of each key residue in the two CheR functions and Tsr signal transduction processes. The completion of this project will reveal the molecular mechanism of functional interaction between CheR and Tsr receptor, shed new lights on understanding E. coli chemotaxis signal transduction, and provide important scientific perspectives on bacterial chemotaxis and molecular mechanisms of transmembrane signaling.