Determining the substrate specificity of ER oxidoreductases

为了使细胞和组织保持健康，它们必须能够制造蛋白质，并且它们制造的蛋白质必须能够正确地发挥作用。细胞具有复杂的机制，以确保当新蛋白质产生时，它们是功能性的，并被运送到正确的位置，无论是在细胞内还是细胞外。该项目将解决细胞如何确保蛋白质正确制造并采用正确形状的一般问题。蛋白质是由一串氨基酸组成的，这些氨基酸卷曲或折叠以形成特征形状或三维结构。只有一个这样的形状是功能性的，细胞通过提供辅助蛋白或伴侣蛋白来帮助这一过程，以确保这种形状被采用。位于细胞内的一个酶家族负责确保某些蛋白质被正确制造并采用正确的形状。然而，人们对这些酶能够帮助哪些蛋白质或它们的确切功能知之甚少。我们将使用一种新开发的技术来识别这些酶中每一种的底物蛋白，并使用这些信息来精确地确定它们在细胞内蛋白质折叠过程中的功能。从这项工作中获得的信息将有助于我们了解细胞产生蛋白质需要什么。更深入地了解蛋白质折叠的要求将有助于我们在试图以重组形式生产蛋白质用于结构生物学研究或医学用途时做出合理的决定。

For cells and tissues to remain healthy they must be able to make proteins and the proteins they make must be able to function correctly. The cell has complex machinery for ensuring that when new proteins are made they are functional and are transported to the correct location, be it within the cell or outside. This project will address the general question of how the cell ensures that proteins are made correctly and adopt the correct shape. Proteins are made as a string of amino acids which coil-up or fold to adopt a characteristic shape or three-dimensional structure. Only one such shape is functional and the cell ensures that this shape is adopted by providing helper proteins or chaperones to aid this process. A family of enzymes that are located within the cell are responsible for ensuring that some proteins are made correctly and adopt the correct shape. However little is known about which proteins these enzymes are able to help or indeed what their exact function is. We will use a newly developed technique to identify the substrate proteins for each of these enzymes and use this information to determine precisely their function during the folding of proteins within the cell. The information gained from this work will help with our attempts to understand what the cell needs to produce proteins. Understanding the requirements for protein folding in more depth will aid us to make rational decisions when we try to produce proteins in a recombinant form for either structural biology studies or for medical uses.