生物膜融合蛋白质分子结构与动力学的时间分辨非线性光谱研究

项目名称： 生物膜融合蛋白质分子结构与动力学的时间分辨非线性光谱研究

项目编号： No.21473177

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 叶树集

作者单位： 中国科学技术大学

项目金额： 96万元

中文摘要： 生物膜融合过程中融合蛋白质分子结构与动力学行为是化学与生物交叉学科中的一个新兴物理化学前沿科学问题，因缺乏表征膜融合过程中的融合蛋白质分子结构的有效手段，目前对膜融合详细机理仍缺乏了解。本项目拟发展一套能同时快速表征界面分子结构与动力学行为的偏振衰减光腔衰荡光谱与飞秒宽带红外和频光谱联用的毫秒尺度时间分辨超快光谱系统，结合申请人最近发展的界面蛋白质酰胺I和酰胺III等多谱带表征技术，以病毒融合蛋白质分子为模型，系统地研究融合多肽与生物膜作用过程，以及膜融合过程中融合蛋白质分子构象和生物膜结构的瞬时变化过程。将融合蛋白质分子结构与融合过程中生物膜中间态结构关联起来，从分子水平上理解融合多肽如何对融合机理产生作用，理解膜融合蛋白质分子如何改变生物膜结构与形状，从而更加深入地认识膜融合过程的本质与规律，最终为研制出能阻止流感、HIV、肝炎等病毒入侵的疫苗以及为设计新的药物传输方法提供新思路。

中文关键词： 生物膜融合蛋白质；分子结构；动力学；时间分辨；非线性光谱

英文摘要： The study on the molecular structure and dynamics of fusion protein during membrane fusion is a novel frontier physical chemistry problem in the interdisciplinarity between chemistry and bioscience. Yet it is still one of the most challenging problems due to lack of effective techniques that can explicitly determine the intermediate molecular structures of fusion protein during membrane fusion. Consequently, the detailed membrane fusion mechanism remains elusive so far. In this project, a time-resolved ultrafast spectroscopy system, which combines polarized evanescent wave cavity ring-down spectroscopy and femtosecond infrared broadband sum frequency generation vibrational spectroscopy, will be developed to synchronously characterize the interfacial molecular structures and dynamics at the millisecond time scale. Using virus fusion proteins as the models, we will apply this time-resolved system to study systematically the interaction between fusion peptide and cell membrane, as well as investigate how the fusion protein conformation and the intermediate structures of cell membrane change during membrane fusion. The molecular structures of fusion protein determined by measuring the amide I, amide II, amide III and Amide A signals of the protein backbone stretching will be correlated to the intermediate structure of cell membrane. Results from this research will provide us with a molecular-level understanding on how the fusion peptides play a key role in membrane fusion and how the fusion protein molecules change the structure and shape of cell membrane, and thus further provide an in-depth insight into the nature and rules of membrane fusion processes. The results from this project will provide important clues to design and develop novel vaccine to prevent the invasion of viruses such as influenza, HIV and hepatitis, as well as design new methods for drug delivery.

英文关键词： Membrane-Fusion Protein;Molecular Structure;Dynamics;Time Resolved;Nonlinear Vibrational Spectroscopy