The network of protein quality control factors in the cell envelope of Escherichia coli

每个细胞都有成千上万种不同的蛋白质，这些蛋白质在丰度和化学性质上差异很大。为了确保所有蛋白质都具有生物活性，定位于适当的细胞区室并以适当的量存在，在进化过程中建立了有效的质量控制机制。质量控制的失败可能会影响细胞生长（癌症，细菌致病性），并可能导致基于蛋白质折叠，定位和降解问题的严重疾病（例如阿尔茨海默病和朊病毒病，囊性纤维化，关节炎）。因此，在分子水平上研究蛋白质质量控制的基本机制具有普遍意义。我们建议使用一个简单的实验系统，细菌细胞包膜，和一个综合的方法，包括遗传学，表型和代谢组学分析和体外生物化学，揭示蛋白质诊断，修复和降解的基本生物学概念。在该项目的第一阶段，我们将通过研究相关细胞组分（即各种分子伴侣、折叠催化剂和蛋白酶）的作用和相互联系来识别和鉴定蛋白质折叠、修复和降解的途径。

Each cell hosts thousands of different proteins that vary greatly in abundance and chemical properties. To ensure that all proteins are biologically active, localised to the proper cellular compartment and are present in appropriate quantity, efficient mechanisms of quality control were established during evolution. The failure of quality control can influence cell growth (cancer, bacterial pathogenicity) and can cause severe diseases that are based on protein folding, localisation and degradation problems (e.g. Alzheimer¿s and prion diseases, cystic fibrosis, arthritis). It is therefore of general relevance to study the fundamental mechanisms of protein quality control on the molecular level. We propose to use a simple experimental system, the bacterial cell envelope, and an integrated approach comprising genetics, phenotype and metabolomic analyses and in vitro biochemistry, to reveal the basic biological concepts governing protein diagnosis, repair and degradation. In phase 1 of the project, we will identify and characterise pathways of protein folding, repair and degradation by studying the roles and interconnections of the relevant cellular components that is the various chaperones, folding catalysts and proteases.