Nitric oxide-sensing H-NOX proteins govern bacterial communal behavior

Abstract

Heme-Nitric oxide/Oxygen binding (H-NOX) domains function as sensors for the gaseous signaling agent nitric oxide (NO) in eukaryotes and bacteria. Mammalian NO signaling is well characterized and involves the H-NOX domain of soluble guanylate cyclase. In bacteria, H-NOX proteins interact with bacterial signaling proteins in two-component signaling systems or in cyclic-di-GMP metabolism. Characterization of several downstream signaling processes has shown that bacterial H-NOX proteins share a common role in controlling important bacterial communal behaviors in response to NO. The H-NOX pathways regulate motility, biofilm formation, quorum sensing, and symbiosis. Here, we review the latest structural and mechanistic studies that have elucidated how H-NOX domains selectively bind NO and transduce ligand binding into conformational changes that modulate activity of signaling partners. Furthermore, we summarize the recent advances in understanding the physiological function and biochemical details of the H-NOX signaling pathways.

Discovery of stimulator binding to a conserved pocket in the heme domain of soluble guanylyl cyclase

“…We therefore characterized stimulator binding to Cb SONO, as well as three previously described H-NOX proteins from Nostoc sp. 7120 (Ns H-NOX), Shewanella oneidensis (So H-NOX), and Shewanella woodyi (Sw H-NOX) (23). IWP-854 labeled all four bacterial H-NOX proteins (Fig.…”

“…7120 (32,33) and Shewanella oneidensis (34). These structures display the same overall fold and provide a solid scaffold for understanding H-NOX structure in sGC function (reviewed in (4,5,23)). The overall H-NOX fold is ~180 residues long and displays an N-terminal sub-domain encompassing residues 1-60, which is dominated by a 3-helix bundle, followed by a larger mixed helix/sheet sub-domain that contains the heme pocket.…”

Microbial Surface Colonization and Biofilm Development in Marine Environments

“…Surface-associated bacteria usually harbor more c-di-GMP regulators than free-living bacteria, presumably as an adaptive strategy (120). O 2 , H 2 O 2 , NO, redox potential, light, sucrose, amino acids, polyamines (such as norspermidine and spermidine), Zn 2ϩ , bile acids, bicarbonate, indole, QS autoinducers, cis-2-dodecenoic acid and cis-11-methyl-dodecenoic acid (unsaturated fatty acids that serve as bacterial diffusible signal factors), and nutritional conditions that cause starvation (or depletion of a specific carbon source such as glucose or glycerol) have been identified as environmental cues that induce the bacterial response via altering the intracellular c-di-GMP concentration (480,(492)(493)(494)(495)(496)(497)(498)(499)(500)(501)(502)(503)(504)(505)(506)(507)(508). However, the vast majority of the environmental signals that modulate the activity of the DGCs and PDEs remain unidentified.…”

Origin and Impact of Nitric Oxide in Pseudomonas aeruginosa Biofilms

“…The two-component system present in Shewanella woodyi comprises the SwH-NOX (H-NOX of S. woodyi) and SwGGDEF-EAL (HaCE [H-NOX-associated c-di-GMP-processing enzyme]) proteins: NO binds to SwH-NOX and regulates the partner protein by simultaneously downregulating its cyclase activity and upregulating the phosphodiesterase activity (89,90). In general, NO binding events in bacterial H-NOX domains seem to cause conformational changes involving the N-terminal helices, which mediate interaction with partner enzymes, such as HaCEs (see above), or control the activity of a dedicated histidine kinase (H-NOX-associated histidine kinase [HnoK]), as seen in Shewanella oneidensis (91), ultimately resulting in changes of c-di-GMP within the cell (88) (Fig. 3).…”