强迫症是一种高致残性的焦虑性神经疾病，全球约2%的人口饱受其折磨,但其发病机制仍不清楚。近年来对于强迫症的研究发现谷氨酸神经突触的信号传导与强迫症有着紧密关联，敲除Sapap3 基因（定位于兴奋性突触后致密区的一类支架蛋白）的小鼠会出现类似强迫症的行为。SAPAP能够与PSD95以及Shank形成三元复合物，进而对谷氨酸神经突触的信号通路起到关键的调控作用。目前对于PSD95/SAPAP间相互作用的机制仍不清楚，研究该相互作用的机制，对于深入了解强迫症的发病机制及设计开发治疗强迫症等神经疾病的药物具有深远的生物学意义。本项目拟利用生物化学、结构生物学方法对PSD95/SAPAP蛋白复合物的相互作用进行详细表征和结构测定，并根据结构靶向设计多肽，从而为了解强迫症发病的分子机理并开发治疗强迫症的药物等相关研究提供结构基础。

OCD (obsessive compulsive disorder), one of the most common and incapacitating psychiatric disorders, affects 2% of the world population. Studies of OCD gain much more focus in recent years, however its pathogenic mechanisms are largely unknown. Recent studies showed that Sapap3-mutant mice exhibit OCD-like behaviors, indicating the glutamatergic synaptic transmission is implicated in OCD pathogenesis. The scaffold protein SAPAP locates in the PSD (postsynapse density) of exciting synapse, and forms a ternary complex together with PSD95 and Shank. The complex plays a key role in regulating the glutamatergic synaptic transmission. Understanding the mechanism of PSD95/SAPAP interaction is important for the study of OCD pathogenesis and treatment. We prepare to characterize the detailed binding mode of PSD95/SAPAP by biochemical methods, and solve the complex structure using structure biological techniques. Our study will provide a solid structural basis for revealing the pathogenic mechanism of OCD, and will shed light on developing new medicines of OCD.