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

蛋白质质量控制对于细胞的适当维护是必不可少的。它确保新合成蛋白质的正确折叠，错误折叠和聚集的蛋白质的重折叠或降解，以及调节蛋白质的受控降解。这些功能由分子伴侣和蛋白水解酶共同完成。该项目将确定ATP依赖的蛋白水解酶底物选择性的分子基础，并确定伴侣和蛋白水解酶之间的关系。主要的焦点将集中在对新的AAA+辅助因子的机制分析上，例如我们最近发现的CLP。对这些蛋白质的详细分析是理解伴侣蛋白和蛋白水解酶(A)如何识别它们的底物和(B)在体内竞争不同底物的关键。

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.