Enzymatic repair of oxidized proteins: a novel quality control in the periplasm – METOXIC

Protein quality control is a vital cellular process. Bacteria are exposed to oxidative stress, both endogenous and exogenous, which eventually damage macromolecules, in particular proteins. We recently identified a new enzymatic system, MsrPQ (standing for methionine sulfoxide reductase), located in the periplasm, which reduces oxidized methionine residues and thereby repair oxidized proteins. METOXIC is an interdisciplinary project that aims at developing a multi-levelled approach of the repair activity of the MsrPQ system such as to reach an integrated view of this new anti-ROS defence. We will focus on the atomic details of the catalytic activity, by identifying determinants within both the substrate and the enzyme, which are required for the reduction to occur. We will investigate the molecular basis of the different genetic circuits regulation MsrPQ synthesis in response to various stresses, specifically copper and bleach. Last, we will aim at assessing the protecting/repairing role of MsrPQ into copper homeostasis and photosynthesis, two processes involving multiple protein ensembles, which could be targeted by reactive chemical species. Because oxidative stress is often connected to redox and bioenergetic metabolism, we will study two bacterial models, Escherichia coli and Rhodobacter sphaeroides, which rely on two different bioenergetic processes, respiration and photosynthesis. The analysis of the MsrPQ repair system in two different species, which evolved in different habitats and faced different stress conditions, will improve our understanding of the stress adaptation response of bacteria in general and of MsrPQ, a new key anti-oxidative stress defence system. Moreover, informations and concepts collected in the course of the project should pave the way for various applications, in biotechnology, bioenergy and might help designing new antibacterial agents.