Structural studies on ER-associated protein quality control mechanisms

ER相关蛋白质量控制机制的结构研究

• 批准号: 2273971
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2273971
• 关键词: Structural; studies; ER; associated; protein

Quality control mechanisms are essential for clearing misfolded, non-functional proteins from the cell. This is especially important in the endoplasmic reticulum (ER) where secretory and cell surface proteins are synthesised. ER-associated degradation (ERAD) is an export pathway for misfolded proteins and comprises of various machinery for the selection, ubiquitination and extraction of membrane proteins from the ER. Its malfunction has been implicated in more than 60 human diseases, examples of which include Alzheimer's and cystic fibrosis. Mammalian ERAD mechanisms are still poorly understood and there has been minimal structural insight provided thus far. This project will take a multidisciplinary approach to characterise ERAD pathways in mammalian cells. Cryo-electron microscopy, biochemical and molecular analysis will be used to identify the molecular details of misfolded protein export.

质量控制机制对于从细胞中清除错误折叠的无功能蛋白质至关重要。这在合成分泌蛋白和细胞表面蛋白的内质网（ER）中尤其重要。ER相关降解（ERAD）是错误折叠蛋白质的输出途径，包括从ER中选择、遍在化和提取膜蛋白的各种机制。它的功能障碍与60多种人类疾病有关，其中包括阿尔茨海默氏症和囊性纤维化。哺乳动物ERAD机制仍然知之甚少，迄今为止提供的结构见解很少。该项目将采用多学科方法研究哺乳动物细胞中的ERAD途径。冷冻电子显微镜、生物化学和分子分析将用于鉴定错误折叠蛋白输出的分子细节。