Bacterial hemerythrin domain-containing oxygen and redox sensors: Versatile roles for oxygen and redox signaling

Abstract

Hemerythrin is an oxygen-binding protein originally found in certain marine invertebrates. Oxygen reversibly binds at its non-heme diiron center, which consists of two oxo-bridged iron atoms bound to a characteristic conserved set of five His residues, one Glu residue, and one Asp residue. It was recently discovered that several bacteria utilize hemerythrin as an oxygen- and redox-sensing domain in responding to changes in cellular oxygen concentration or redox status, and immediately adapt to these environmental changes in order to maintain important physiological processes, including chemotaxis and c-di-GMP synthesis and degradation. This Mini Review focuses on the recent progress made on structural and functional aspects of these emerging bacterial hemerythrin domain-containing oxygen and redox sensors, revealing characteristic features of this family of proteins.

Keywords: c-di-GMP; hemerythrin; methyl-accepting chemotaxis protein; non-heme diiron; oxygen senor; redox sensor; signaling.

FIGURE 1

Reaction of the non-heme diiron center and domain structure of bacterial hemerythrin domain-containing sensors. (A) Reaction scheme for the non-heme diiron center. Upper and lower irons are Fe1 and Fe2, respectively. The iron ligand residues are omitted for the sake of clarity. The oxy form is a transient intermediate in reactions involving bacterial hemerythrin domain-containing sensors. (B) Domain structures of bacterial hemerythrin domain-containing sensors that have been characterized so far, namely D. vulgaris DcrH (UniProt ID: Q726F3), V. cholerae Bhr-DGC (UniProt ID: Q9KSP0), Ferrovum sp. PN-J185 Bhr-HD-GYP (UniProt ID: A0A149VUS3), and A. cellulolyticus P_1B-5-ATPase (UniProt ID: A0LQU2). Transmembrane helices are shown as black rectangles. In DcrH, HAMP, MCP, and hemerythrin domains are located in cytoplasm, whereas the region between two transmembrane helices is located in periplasm. In P_1B-5-ATPase, actuator, ATP-binding, and hemerythrin-like domains are located in cytoplasm. The double-headed arrow represents a length corresponding to 100 amino acid (aa) residues. Hr, hemerythrin.

FIGURE 2

Structural features of the hemerythrin domain of the bacterial hemerythrin domain-containing sensor DcrH. (A) Structural comparison of the hemerythrin domain in its met (green, PDB entry 2AWY) and deoxy (cyan, PDB entry 2AWC) forms. The N-terminal loop is circled. (B) An enlarged depiction of the non-heme diiron center in its met form (PDB entry 2AWY). Iron atoms and bridging oxo are shown as orange and red spheres, respectively. Chloride (green sphere) is bound to Fe2 in the non-heme diiron center.