Structures of biological heme-based sensors of oxygen

Abstract

Since their initial discovery some 30 years ago, heme-based O2 sensors have been extensively studied. Among many other lessons, we have learned that they have adapted a wide variety of folds to bind heme for O2 sensing, and they can couple those sensory domains to transducer domains with many different activities. There is no question that we have learned a great deal about those systems by solving X-ray structures of the truncated pieces of larger multi-domain proteins. All of the studies have, for example, hinted at the importance of protein residues, which were further investigated, usually by site-directed mutagenesis of the full-length proteins together with physico-chemical measurements and enzymatic studies. The biochemistry has suggested that the sensing functions of heme-based O2 sensors involve not only the entire proteins but also, and quite often, their associated regulatory partners and targets. Here we critically examine the state of knowledge for some well-studied sensors and discuss outstanding questions regarding their structures. For the near future, we may foresee many large complexes with sensor proteins being solved by cryo-EM, to enhance our understanding of their mechanisms.