Nitrogen, a gasocrine signal, is sensed via gas-sensing gasoreceptor proteins such as Escherichia coli FNR protein

Understanding how organisms communicate is a fundamental question in biology and marks an evolutionarily important milestone. Organisms largely communicate via gas-based gasocrine, light-based photocrine, sound-based sonocrine, mineral/metal-based metallocrine, water-based aquacrine, and thermal radiation-based thermocrine signaling.¹ Due to the importance of gasocrine signaling for biotic life, how organisms can sense gasocrine signals such as O₂ (oxygen) via O₂-sensing protein gasoreceptors (or sensors) has been largely investigated in microorganisms.^2,3 Even though nitrogen (N₂) is also one of the gasocrine signals, to the best of my knowledge and few other leading experts on nitrogen fixation and nitric oxide-dependent signaling, how organisms sense nitrogen per se is still unknown. I recently proposed that N₂ is likely sensed indirectly via ammonia-sensing proteins (gasoreceptors).⁴ But there must be other proteins that can sense N₂ per se. Just as the FeMo (iron-molybdenum) cofactor in nitrogenase can directly bind N₂, other FeMo-binding proteins with signaling domains may function as N₂-sensing proteins. Additionally, N₂ can also bind to Fe-S (nonheme iron-sulfur) clusters.⁵ But then if N₂ can bind to Fe-S clusters, this raises an important question on the interpretation of all the Fe-S-protein related experiments that were performed under N₂-rich anerobic conditions in which N₂ was not considered as the ligand but merely as an anerobic environment-inducing agent. For instance, the Escherichia coli Fe-S cluster-based dimeric transcription factor FNR (fumarate and nitrate reductase) can bind to specific DNA regions (FNR consensus motifs) under N₂-rich anerobic condition but loses it dimerization state and DNA-binding ability under O₂-rich condition.^6–8  But FNR is only addressed as an ‘oxygen-sensing protein or oxygen sensor’ or as ‘global anaerobic transcription factor’ and not as a N₂-sensing protein. If the anerobic-specific DNA-binding transcriptional activity via FNR dimerization state is due to either N₂-interaction with FNR-bound Fe-S cluster or non-Fe-S salt bridge⁹, FNR is merely an N₂ gas (solute)-sensing gasoreceptor protein. Orthologues of FNR or other N₂-binding proteins with additional signaling domains are very likely putative N₂-sensing gasoreceptor proteins. Systemically identifying N₂- or other gas-sensing gasoreceptor proteins will help us understand gasocrine signaling and its role in civilizational diseases, antibiotic resistance, agricultural yields, causes for climate change and global warming. 

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