白细胞介素1受体家族胞内TIR结构域介导信号转导的结构基础

IL-1受体（IL-1R）胞内含有一个TIR结构域，隶属于TIR超家族。在IL-1介导的炎症反应中发挥重要的作用。IL-1结合到IL-1R的胞外区，使得胞内的TIR结构域之间相互靠近，招募下游的适配体蛋白MyD88，最终调控下游基因的转录。本课题组在IL-1/IL-1R胞外区的结构与功能方面积累了丰富的经验。目前，对于IL-1R胞内TIR-TIR之间是如何协作参与到IL-1信号转导过程仍然是非常不清楚的。本研究将围绕以下两个方面的内容进行研究：（1）解析IL-1R-TIR结构域的结构，探究IL-1R-TIR结构域的功能决定区；（2）解析IL-1β/IL-1RI/IL-1RAcP三元复合物结构，揭示IL-1R胞内TIR结构域介导信号转导的结构基础。我们的研究将进一步加深我们对TIR结构域介导信号转导分子机制的理解，为靶向IL-1R-TIR结构域的药物开发提供帮助。

Interleukin 1 (IL-1) receptors (IL-1Rs), containing a TIR domain in the intracellular space, belong to the TIR superfamily and play important roles in IL-1 cytokines mediated inflammatory response. IL-1 cytokines bind to the extracellular domain of IL-1Rs, leading the intracellular TIR domains close to each other, thus recruiting the downstream adaptor protein MyD88 and regulating the transcription of downstream genes. Our research group has accumulated rich experience in the structure and function of IL-1/IL-1R extracellular domain. At present, it still remains unclear about how IL-1R-TIR cooperates with each other to participate in IL-1 signal transduction. This study will focus on the following two aspects :(1) determine the structures of TIR in IL-1R family to explore the functional determinants; (2) determine the complex structure of IL-1β/IL-1RI/IL-1RAcP to reveal the structural basis of IL-1R-TIR-mediated signal transduction. Our study will enhance our understanding of the molecular mechanisms of TIR domain-mediated signal transduction and aid with drug development targeting the IL-1R-TIR domain.