Heme-based sensors: defining characteristics, recent developments, and regulatory hypotheses

J Inorg Biochem. 2005 Jan;99(1):1-22. doi: 10.1016/j.jinorgbio.2004.11.006.


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 four broad families comprising more than 50 sensors. Heme-based sensors so far feature four different types of heme-binding modules: the heme-binding PAS domain, globin-coupled sensor (GCS), CooA, and heme-NO-binding (HNOB). The transmitters for coupling to such heme-binding domains include histidine protein kinases, cyclic nucleotide phosphodiesterases, chemotaxis methyl-carrier protein receptors, and transcription factors of the basic helix-loop-helix and helix-turn-helix classes. Some well-studied sensors are the FixL, EcDos, AxPDEA1, NPAS2, HemAT-Bs, HemAT-Hs, CooA, and sGC proteins. This review elaborates the defining characteristics of heme-based sensors, examines recent developments on those proteins, and discusses the regulatory hypotheses proposed for those sensors. A general, "helix-swap", model is also proposed here for signal transduction by PAS domains.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biosensing Techniques
  • Carbon Monoxide / chemistry
  • Hemeproteins / chemistry*
  • Hemeproteins / classification
  • Hemeproteins / genetics
  • Hemeproteins / metabolism*
  • Models, Molecular
  • Nitric Oxide / chemistry*
  • Oxidation-Reduction
  • Oxygen / chemistry
  • Phylogeny
  • Protein Binding
  • Protein Conformation
  • Signal Transduction / physiology*


  • Hemeproteins
  • Nitric Oxide
  • Carbon Monoxide
  • Oxygen