Analysis of the proteostasis network and the thermostability of the proteome

蛋白质稳态网络和蛋白质组热稳定性分析

• 批准号: RGPIN-2016-04248
• 负责人: Mayor, Thibault
• 金额: $ 3.93万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629152
• 关键词: Analysis; proteostasis; network; thermostability; proteome

Proteins are central components of our cells. Each protein typically folds or adopts a specific three-dimensional structure, also called native state, that is required for the protein to be functional and stable. The protein folding field witnessed tremendous advances in the past 50 years. Notably, it first became clear that the information required for folding is contained within the protein sequence. It was then discovered that folding is often assisted by chaperones that are specialized molecular machines. A major challenge is now to determine how the combination of these two actions leads to a stable proteome, which is the ensemble of all proteins in the cell. While chaperone proteins can be assessed on an individual basis, thanks to a myriad of elegant and sophisticated biochemical assays, it remains difficult to translate this knowledge into the cellular context, in which millions of different proteins cohabit in a very confined environment. We therefore need to develop new systems-wide approaches and tools to determine how the individual chaperones contribute to the overall stability of the proteome.

蛋白质是我们细胞的核心组成部分。每种蛋白质通常折叠或采用特定的三维结构，也称为天然状态，这是蛋白质具有功能和稳定所必需的。蛋白质折叠领域在过去的50年里取得了巨大的进步。值得注意的是，首先变得清楚的是，折叠所需的信息包含在蛋白质序列中。随后发现折叠通常由分子伴侣（专门的分子机器）辅助。现在的一个主要挑战是确定这两种作用的组合如何导致稳定的蛋白质组，这是细胞中所有蛋白质的集合。虽然伴侣蛋白可以在个体的基础上进行评估，但由于无数优雅而复杂的生化测定，仍然难以将这些知识转化为细胞环境，其中数百万种不同的蛋白质共存于非常有限的环境中。因此，我们需要开发新的系统范围的方法和工具，以确定如何个别分子伴侣有助于蛋白质组的整体稳定性。