Structures of biological heme-based sensors of oxygen.

Since their initial discovery some 30 years ago, heme-based O 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 O 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 O 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.