Haem-based Sensors of Nitric Oxide

Nitric oxide (NO) detection and signalling are widely mediated by haemoproteins in eukaryotes and bacteria. This review highlights the ligand-binding properties, activation mechanisms, and structures of six proteins that have been classified as haem-based NO-sensing proteins: sGC, H-NOX, YybT, E75, NosP, and DNR. sGC is a eukaryotic haem-based sensor that responds to NO to catalyse the production of the ubiquitous secondary messaging signalling molecule cGMP. Much of the progress toward elucidating the NO activation mechanism of sGC has been achieved through the study of bacterial haem-nitric oxide and oxygen (H-NOX) binding proteins. H-NOX proteins are capable of influencing downstream signal transduction in several bacterial species; however, many bacteria that respond to nanomolar concentrations of NO do not contain an annotated H-NOX domain. Of all bacterial species, NO signalling has been most frequently investigated in Pseudomonas aeruginosa, which do not encode an H-NOX domain, and so several receptors of NO have been suggested in this species. Most recently, a newly discovered family of NO-sensing proteins (NosP) was demonstrated to be a mediator of a histidine kinase signal-transduction pathway in P. aeruginosa. NosP proteins are widely conserved in bacteria but have thus far only been characterized in P. aeruginosa. Additionally, a transcriptional regulator called DNR (dissimilative nitrate respiration regulator) has been shown to be a haem-based NO receptor that controls anaerobic denitrification in P. aeruginosa. Another putative bacterial haem-based NO sensor, the cyclic-di-AMP-specific phosphodiesterase YybT is widely distributed across the firmicutes phylum and has been implicated in bacterial survival. Finally, a putative NO sensor in insects, E75, is a haem-based transcriptional regulator. sGC, H-NOX, YybT, E75, NosP, and DNR are discussed in more detail.