融合蛋白ICOSIg的三维结构模建的研究  

Study on the Molecular Modeling of ICOSIg Fusion Protein

作　　者：许雪青[1] 王丰[2] 白云[1] 王璞[1] 段文元[1] 姜曼[3] 黎万玲[3] 

机构地区：[1]中国人民解放军第三军医大学医学遗传教研室,重庆400038 [2]中国人民解放军第三军医大学西南医院检验科,重庆400038 [3]中国人民解放军第三军医大学全军免疫学研究所,重庆400038

出　　处：《中国生物工程杂志》2005年第4期69-77,共9页China Biotechnology

基　　金：国家自然科学基金资助项目(300300170)

摘　　要：目的:利用结构相似性的序列比对来模建ICOSIg的三维结构,分析其可能的结合位点,为 改造ICOSIg的突变体,提高其结合活性提供理论基础。方法:利用生物信息学手段分析ICOS所 属CD28家族各成员分子的结构域,通过基于结构相似的序列比对,以空间结构已经得到解析的 CTLA4为模板,利用同源模建的方法,模建ICOS膜外区的空间结构。进一步地以人IgG2和 CTLA4为模板,模建了ICOSIg全长的空间结构。在此基础上,结合氨基酸特性,分析其可能的功 能位点。结果:FDPPPF及KTKGSGN基序可能是ICOSIg的功能结合位点。结论:模建了ICOSIg 的空间结构,分析了其可能结合位点,为突变ICOSIg提高其亲和力提供了线索。Objective: To model the structure of ICOSIg and analysis its binding site. Methods: The domain of molecules in CD28 family was predicated with bioinformatics means,and members in the family was aligned based on their domain similarity. After that, used CTLA-4 as the template, the structure of extracellular region of ICOS was homology modeled. And then, used IgG2 and CTLA4 as the templates, the structure of ICOSIg fusion protein was also modeled. Base on the structure model, the binding site of ICOSIg was analysised. Result: FDPPPF and KTKGSGN motifs were predicted as the binding site. Conclusion: The ICOSIg structure was modeled and its binding site was analysed. These results give us useful clue on the study of high avidity ICOSIg mutants.

关 键 词：融合蛋白 CTLA4 空间结构 构模 结合位点 序列比对 结构相似性 生物信息学 三维结构 理论基础 结合活性 CD28 同源模建 IgG2 功能位点 突变体 结构域 氨基酸 亲和力 模板 

分 类 号：Q78[生物学—分子生物学] Q753