Chapter 2 - A Surfeit of Biological Heme-based Sensors

Abstract

In a great variety of organisms throughout all kingdoms of life, the heme-based sensor proteins are the key regulators of adaptive responses to fluctuating oxygen, carbon monoxide, and nitric oxide levels. These signal transducers achieve their responses by coupling a regulatory heme-binding domain to a neighboring transmitter. The past decade has witnessed an explosion in the numbers of these modular sensory proteins known, from just two recognized members, FixL and soluble guanylyl cyclase (sGC), to six broad families comprising more than 100 sensors. Heme-based sensors so far feature six different types of heme-binding modules: the heme-binding PAS domain, globin-coupled sensor (GCS), CooA, heme-NO-binding (HNOB) domain, heme-binding GAF domain, and heme-associated ligand-binding domains (LBD) of the nuclear-receptor class. The transmitters for coupling to such heme-binding domains include protein-histidine kinases, serine-threonine kinases, nucleotide cyclases, cyclic-nucleotide phosphodiesterases, chemotaxis methyl-carrier protein receptors, and transcription factors of the basic helix-loop-helix, helix-turn-helix, and zinc-finger classes. Some well-studied sensors are the FixL, Ec Dos, Ax PDEA1, NPAS2, HemAT, CooA, sGC, Tar4, DevS, DosT and E75 proteins. This chapter elaborates the defining characteristics of heme-based sensors, examines the advances on those proteins, and discusses the regulatory hypotheses postulated for those sensors. A general, “helix-swap,” model is also proposed for signal transduction by PAS domains.