The crystal structure of the global anaerobic transcriptional regulator FNR explains its extremely fine-tuned monomer-dimer equilibrium

The structure of the dimeric holo-fumarate and nitrate reduction regulator (FNR) from Aliivibrio fischeri has been solved at 2.65 A degrees resolution. FNR globally controls the transition between anaerobic and aerobic respiration in facultative anaerobes through the assembly/degradation of its oxygen- sensitive [4Fe-4S] cluster. In the absence of O-2, FNR forms a dimer and specifically binds to DNA, whereas in its presence, the cluster is degraded causing FNR monomerization and DNA dissociation. We have used our crystal structure and the information previously gathered from numerous FNR variants to propose that this process is governed by extremely fine-tuned interactions, mediated by two salt bridges near theamino-terminal cluster-binding domain and an imperfect coiled-coil dimer interface. [4Fe-4S] to [2Fe-2S] cluster degradation propagates a conformational signal that indirectly causesmonomerization by disrupting the first of these interactions and unleashing the unzipping of the FNR dimer in the direction of the carboxyl-terminal DNA binding domain.