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研究重组人协同刺激分子CD137配体(rhCD137L)蛋白与其鼠源受体CD137(mCD137)发生相互作用的结构基础。分别以小鼠核因子受体激活剂RANK蛋白和人CD137L的X-射线晶体结构为模板,应用DiscoveryStudio(DS)Modeling 2.5软件同源模建mCD137和rhCD137L的三维结构模型;进行能量优化后,采用Ramachan-dran图和Profiles 3D对模建结构进行合理性评估;通过ZDOCK模块进行分子对接,预测rhCD137L-mCD137的候选结合结构域。结果表明,rhCD137L中存在多个可与mCD137发生相互作用的候选结合位点,其中包括D80-A82、L84、以及参与其与人源受体CD137发生相互作用的A’B Loop环(Q98-T130)和Q230。与已知人源CD137L-CD137间的相互作用不同,rhCD137L还与mCD137形成了2个氢键。CD137L虽然可以与鼠源受体发生相互作用,但与人源受体的结合模式并不完全相同。该结果为今后深入研究CD137通路发挥协同刺激作用的信号体系以及基于该信号途径新型分子靶向药物的设计提供了理论基础。
To study the structural basis of the interaction between the recombinant human costimulatory molecule CD137 ligand (rhCD137L) and its murine receptor CD137 (mCD137). The three-dimensional structure models of mCD137 and rhCD137L were homologously modeled using DiscoveryStudio (DS) Modeling 2.5 software using the X-ray crystal structure of the mouse nuclear factor receptor activator RANK protein and human CD137L as templates. After energy optimization, Ramachan-dran maps and Profiles 3D were used to evaluate the rationality of the mimicking structures. The molecular docking of the ZDOCK module was used to predict the candidate binding domains of rhCD137L-mCD137. The results showed that there are multiple candidate binding sites in rhCD137L that can interact with mCD137, including D80-A82, L84, and the A’B Loop (Q98-T130) involved in its interaction with the human receptor CD137 ) And Q230. Unlike the known human CD137L-CD137 interaction, rhCD137L also forms two hydrogen bonds with mCD137. Although CD137L can interact with murine receptors, the pattern of binding to human receptors is not exactly the same. The results provide a theoretical basis for further study of the signal system that synergistically stimulates the CD137 pathway and the design of novel molecular targeted drugs based on the signaling pathway.