Structural mechanism of cellular redox switch proteins

다국어 초록 (Multilingual Abstract)

Reactive oxygen species(ROS) are produced as byproducts of aerobic respiration and toxic to cells. However, ROS are used also as crucial cellular messengers in growth factor signal transduction, brain function, immune response and apoptosis. Recent studies indicate that there are intricate intracellular networks linking harmful ROS production and critical cellular regulatory functions. The cellular responses to altered levels of ROS involve redox switch proteins whose activities are regulated by oxidation. We determined crystal structures of the prototype redox switch proteins, OxyR and Hsp33. For OxyR, we obtained the structures before(reduced form) and after(oxidized form) reaction with ROS. For Hsp33, we determined the structure in its constitutively active form and carried out a series of biochemical and mutational analyses to elucidate the switch. From the structures of OxyR and Hsp33, and subsequent biochemical and mutational studies, we were able to understand their redox switch principles that should be applicable to other redox switch proteins. We showed that ROS-mediated disulfide bond formation between distant cysteines lead to fundamental structural transitions within domain and between subunits. These structural transitions, which were unexpected and observed for the first time, support important and active roles of ROS in many important physiological processes.