LAUSR

The cellular redox state of organisms continues to fluctuate during the metabolism. All organisms have various sensors that help detect and adapt to changes in the redox state. Nicotinamide adenine dinucleotides (NAD+/NADH), which are involved in various cellular metabolic activities as cofactors, have been revealed as the key molecules sensing the intra-cellular redox state. The Rex family members are well conserved transcriptional repressors that regulate the expression of respiratory genes by sensing the redox state according to the intra-cellular NAD+/NADH balance. Herein, we reported crystal structures of apo and NAD+- and NADH-bound forms of Rex from Thermotoga maritima to analyse the structural basis of transcriptional regulation depending on either NAD+ or NADH binding. The different orientation of the reduced nicotinamide group to helix α9 caused the rearrangement of N-terminal DNA binding domain, thus resulting in closed form of Rex to dissociate from cognate DNA. The structural data of Rex from T. maritima also support the previous redox-sensing mechanism models of Rex homologues.