Roles of biological heme-based sensors of O₂ in controlling bacterial behavior

The heme cofactor is found across all domains of life, serving a variety of purposes, such as gas transport, catalysis of reactions, and gas sensing. Heme-based gas sensors bind NO, CO, and O₂, modulating cellular responses to these ligands. The widespread nature of heme proteins and the importance of oxygen to most life forms make them an intriguing system to investigate the role of heme proteins and bacterial oxygen response. Bacteria use various classes of heme sensors to detect oxygen signals, including heme-containing Per-Arnt-Sim (hPAS), and sensor globin domain-containing proteins. Globin coupled sensor (GCS) proteins have emerged as another widespread heme-based O₂ sensing protein family, providing insights into stabilization of O₂ binding and ligand-selective signaling. GCS proteins also are useful as models for intracellular cyclic-di-guanosine monophosphate (c-di-GMP) signaling, as the most extensively studied group of GCS proteins contain diguanylate cyclase (DGC) output domains, which synthesize c-di-GMP upon ligand binding. These proteins, such as Escherichia coli EcDosC (Direct Oxygen Sensor Cyclase), Pectobacterium carotovorum PccDgcO, and Bordetella pertussis BpeGReg, have been investigated regarding their heme characteristics, biochemistry, and roles in modulating bacterial response to O₂. In addition, the interaction between the E. coli hPAS protein DosP and the GCS DosC highlight the complex systems used to control downstream bacterial response to environmental oxygen.