Investigating How Inter-domain Interactions Influence The Protein Folding Process

在20世纪60年代早期，安芬森奠定了成为蛋白质生物化学基石的教条的基础：即蛋白质的天然折叠是由其氨基酸序列决定的。然而，这忽略了结构域间相互作用在多结构域蛋白折叠中的作用。根据定义，蛋白质结构域能够独立折叠成其功能折叠，但邻近结构域的存在也必须影响蛋白质折叠。我的研究计划的主要目的是提供定量的分子水平描述：a)结构域间相互作用如何促进多结构域蛋白质的整体稳定性；B)这些结构域间相互作用如何影响蛋白质折叠机制。我建议通过研究酵母中Otu1酶的折叠来研究这些相互作用的意义

In the early 1960s, Anfinsen laid down the foundations of the dogma that has become the cornerstone of protein biochemistry: namely, that the native fold of a protein is determined by its amino acid sequence. However, this neglects the role that inter-domain interactions play in the folding of multi-domain proteins. Protein domains by definition are capable of folding into their functional folds independently, but the presence of neighboring domains must also affect the protein fold. The major aim of my research program is to provide a quantitative molecular-level description of: a) how inter-domain interactions contribute to the overall stability of multi-domain proteins; b) how these inter-domain interactions influence the protein folding mechanism. I propose to investigate the significance of these interactions by studying the folding of the enzyme Otu1 from the yeast