AAA+ proteases: substrate binding, translocation and modulation by novel adaptor proteins

蛋白质质量控制对细胞的正常维持至关重要。它确保新合成蛋白质的正确折叠，错误折叠和聚集蛋白质的再折叠或降解，以及调节蛋白的受控降解。这些功能是由分子伴侣和蛋白酶共同完成的。该项目将定义atp依赖性蛋白酶的底物选择性的分子基础，并确定伴侣蛋白和蛋白酶之间的关系。一个主要的焦点将是我们最近发现的新型AAA+辅助因子（如ClpS）的机制分析。对这些蛋白质的详细分析对于理解伴侣蛋白和蛋白酶如何(A)识别它们的底物以及(b)在体内竞争不同的底物至关重要。

Protein quality control is essential for the proper maintenance of the cell. It ensures the correct folding of newly synthesised proteins, the refolding or degradation of misfolded and aggregated proteins, and the controlled degradation of regulatory proteins. These functions are collectively performed by molecular chaperones and proteases. This project will define the molecular basis of substrate selectivity for ATP-dependent proteases and determine the relationship between chaperones and proteases. A major focus will be directed towards the mechanistic analysis of novel AAA+ cofactors such as ClpS, which we recently discovered. A detailed analysis of such proteins is central to understanding how chaperones and protease (a) recognize their substrates and (b) compete for different substrates in vivo.