Structure-function analysis of DegP

点击翻译按钮获取中文摘要

The widely conserved HtrA family of serine proteases is involved in extracytoplasmic protein quality control. Two well studied family members, E. coli DegP and DegS are key players of the unfolded protein response performing protective and regulatory roles. DegS senses protein folding defects and initiates a signaling cascade that controls the activity of dozens of stress promoters including degP. DegP switches between molecular chaperone and protease functions channelling damaged proteins into either repair or degradation pathways. Recent work revealed that DegP switches also between three oligomeric states (hexamer, 12 and 24mer) and that different functional and architectural features might be interconnected. This research proposal aims at characterising in detail the underlying molecular mechanisms determining the switch of oligomeric state and their physiological consequences using genetic, biochemical and structural approaches. These studies will contribute to our understanding of the general principles of stress sensing, protein repair and degradation in the bacterial cell envelope.