模型蛋白淀粉纤维化过程中铜、锌等二价金属离子微观作用机制的拉曼光谱研究

蛋白质淀粉纤维化可以导致众多神经退行性疾病，而不同离子对该过程的促进或抑制作用迥然不同。铜、锌等二价金属离子不仅是人体的重要组成元素，而且也是许多生命体活动的信息和能量载体，它们与淀粉纤维样的形成可能存在着重要的内在关联。本项目中，我们将综合应用拉曼光谱、红外光谱等多种谱学手段，原位地测量这些金属离子与不同模型蛋白质分子的作用类型和位点，以及随变性过程二级和三级结构的动力学演化和形貌变化，从而揭示Cu2+、Zn2+等二价金属离子在鸡蛋清溶菌酶（HEWL）和人体血清蛋白（HSA）等模型蛋白质淀粉纤维化过程中的微观作用机制，增强对相关化学物理过程规律（Hofmeister序列）的认识，为相关药物开发提供新的思路和新的靶点。

Amyloid fibrillation of proteins can lead to many neurodegenerative diseases, in which various ions show the entirely different effects of promotion or inhibition. The divalent metal ions such as Cu2+ and Zn2+ are not only important elements of human, but also the carriers of information and energy for life activities. There might be an important correlation between them and the formation of amyloid fibrils. In this project, we will perform a comprehensive spectral investigation such as Raman spectroscopy, to measure in situ the interactions and sites of these metal ions on various model proteins, as well as the kinetics of secondary and tertiary structures and the corresponding morphological changes. Thus, the action mechanisms of these divalent metal ions in amyloid fibrillation of model proteins such as egg white lysozyme (HEWL) and human serum protein (HSA), will be clarified, improving our knowledge of the related rules like Hofmeister sequence and providing new ideas and new targets for developing drugs.