应用自制生物原子力显微镜研究FGF21/FGFR1c复合物的识别结合特性

项目名称： 应用自制生物原子力显微镜研究FGF21/FGFR1c复合物的识别结合特性

项目编号： No.21505139

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 张晶

作者单位： 中国科学院合肥物质科学研究院

项目金额： 21万元

中文摘要： 成纤维细胞生长因子21（FGF21）具有与胰岛素类似的糖脂代谢调节能力，但在用药副作用方面优于胰岛素，有望成为治疗II型糖尿病的新一代蛋白质类药物。但是，目前对FGF21调控II型糖尿病代谢的分子机理仍不清楚，尤其是缺乏在活细胞表面FGF21与其靶向受体FGFR1c之间的识别作用力以及识别过程动力学方面的研究数据，极大地阻碍了对其分子作用机理的深入研究。本项目中，申请人基于利用商业原子力显微镜（AFM）研究多种药物分子的识别结合特性而积累的理论和实践经验，以及本课题组成功研制的具有自主知识产权的高灵敏新测法的高Q快调幅磁力显微镜（HQAM-MFM），拟将HQAM-MFM改装为生物HQAM-AFM，并应用于在活细胞表面原位探测FGF21/FGFR1c复合物在单分子层面上的识别作用力和识别动力学过程，为在更深层次上阐释FGF21的分子识别机制提供支持。

中文关键词： 原子力显微镜；生物分子；单分子力谱；分子识别；机理研究

英文摘要： Because of its potent ability to regulate glucose, lipid and energy homeostasis, and its superiority compared to insulin in drug side effect, fibroblast growth factor 21 (FGF21) has generated a lot of interest recently as a potentially powerful therapeutic agent for treating the type II diabetes. However, relative little is known about the interaction force and interaction dynamics of FGF21 and its receptor FGFR1c at the plasma membrane, which is important for the molecular elucidation of the FGF21/FGFR1c interaction and its function in the regulation of the type II diabetes. In this work, on the base of the experience I have accumulated during the studies of the interaction properties of several kinds of cancer targeted drugs with a commercial AFM setup, and the magnetic force microscope our group constructed successfully with a higher speed amplitude modulation using tips with high Q values (HQAM-MFM), we will do slight improvements of the core of the microscope to transfer the HQAM-MFM into a new biological HQAM-AFM. The new AFM setup will be used to study the binding property of the FGF21/FGFR1c complex at the single molecular level on living cell surface, paving the way for the deeper research revealing the regulation mechanism behind the specific binding of the FGF21/FGFR1c complex.

英文关键词： atomic force microscope;biological molecule;single molecular force spectroscopy;molecular recognition;mechanism study