Structural Insight into H‐NOX Gas Sensing and Cognate Signaling Protein Regulation

Abstract

Heme‐nitric oxide/oxygen binding (H‐NOX) proteins are a family of gas‐binding hemoproteins that bind diatomic gas ligands such as nitric oxide (NO) and oxygen (O2). In bacteria, H‐NOXs are often associated with signaling partners, including histidine kinases (HKs), diguanylate cyclases (DGCs) or methyl‐accepting chemotaxis proteins (MCPs), either as a stand‐alone protein or as a domain of a larger polypeptide. H‐NOXs regulate the activity of cognate signaling proteins through ligand‐induced conformational changes in the H‐NOX domain and protein/protein interactions between the H‐NOX and the cognate signaling partner. This review summarizes recent progress toward deciphering the molecular mechanism of bacterial H‐NOX activation and the subsequent regulation of H‐NOX‐associated cognate sensor proteins from a structural and biochemical point of view.

Solution structures of the Shewanella woodyiH‐NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP‐051

“…Heme‐nitric oxide/oxygen binding (H‐NOX) domains are gas‐sensing hemoproteins that bind dissolved gases and induce signaling responses in a wide variety of organisms. In prokaryotes, H‐NOX sensors function as both stand‐alone proteins and as members of multidomain proteins, and respond to nitric oxide (NO), oxygen and potentially other ligands such as carbon monoxide (CO) to induce a signaling cascade 1,2 . Obligate anaerobes use H‐NOX domains to escape dioxygen as part of a methyl‐accepting chemotaxis system while a variety of bacteria use stand‐alone H‐NOX proteins to sense NO and repress biofilm formation through lowering cyclic di‐GMP levels.…”

“…In prokaryotes, H-NOX sensors function as both stand-alone proteins and as members of multidomain proteins, and respond to nitric oxide (NO), oxygen and potentially other ligands such as carbon monoxide (CO) to induce a signaling cascade. 1,2 Obligate anaerobes use H-NOX domains to escape dioxygen as part of a methyl-accepting chemotaxis system while a variety of bacteria use stand-alone H-NOX proteins to sense NO and repress biofilm formation through lowering cyclic di-GMP levels. In the latter case, H-NOX proteins may participate in a two-component signaling cascade, inhibiting a histidine kinase that stimulates a cyclic di-GMP synthase, or by directly stimulating the phosphodiesterase activity, and inhibiting the cyclase activity, of a cyclic di-GMP synthase/phosphodiesterase fusion protein.…”

Structural insights into the mechanism of oxidative activation of heme-free H-NOX from Vibrio cholerae

“…Structural studies on the H-NOX family have made significant progress toward understanding the mechanisms of signal transduction [65]. Briefly, NO binding to the heme iron displaces the proximal His ligand, relieving heme distortion imposed by steric constraints with a conserved, proximal Pro residue.…”

Solution structures of theShewanella woodyiH-NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP-051

“…H-NOX domains are gas-sensing hemoproteins that bind dissolved gases and induce signaling responses in a wide variety of organisms. In prokaryotes, H-NOX sensors function as both stand-alone proteins and as members of multidomain proteins, and respond to nitric oxide, oxygen or potentially other ligands to induce a signaling cascade [1,2]. Obligate anaerobes use H-NOX domains to escape dioxygen as part of a methyl-accepting chemotaxis system while a variety of bacteria use stand-alone H-NOX proteins to sense nitric oxide and repress biofilm formation through lowering cyclic di-GMP levels.…”