Reassessing the Structure and Function Relationship of the O2 Sensing Transcription Factor FNR

Significance: The Escherichia coli regulatory protein fumarate nitrate reduction (FNR) mediates a global transcriptional response upon O-2 deprivation. Spanning nearly 40 years of research investigations, our understanding of how FNR senses and responds to O-2 has considerably progressed despite a lack of structural information for most of that period. This knowledge has established the paradigm for how facultative anaerobic bacteria sense changes in O-2 tension. Recent Advances: Recently, the X-ray crystal structure of Aliivibrio fischeri FNR with its [4Fe-4S] cluster cofactor was solved and has provided valuable new insight into FNR structure and function. These findings have alluded to the conformational changes that may occur to alter FNR activity in response to O-2. Critical Issues: Here, we review the major features of this structure in context of previously acquired data. In doing so, we discuss additional mechanistic aspects of FNR function that warrant further investigation. Future Directions: To complement the [4Fe-4S]-FNR structure, the structures of apo-FNR and FNR bound to DNA or RNA polymerase are needed. Together, these structures would elevate our understanding of how ligation of its [4Fe-4S] cluster allows FNR to regulate transcription according to the level of environmental O-2. Antioxid. Redox Signal. 00, 000-000.