The structural adaptability of the globin fold has been highlighted by the recent discovery of the 2-on-2 haemoglobins, of neuroglobin and cytoglobin. Protoglobin from Methanosarcina acetivorans C2A-a strictly anaerobic methanogenic Archaea-is, to the best of our knowledge, the latest entry adding new variability and functional complexity to the haemoglobin (Hb) superfamily. Here, we report the 1.3 Å crystal structure of oxygenated M. acetivorans protoglobin, together with the first insight into its ligand-binding properties. We show that, contrary to all known globins, protoglobin-specific loops and an amino-terminal extension completely bury the haem within the protein matrix. Access of O 2 , CO and NO to the haem is granted by the protoglobinspecific apolar tunnels reaching the haem distal site from locations at the B/G and B/E helix interfaces. Functionally, M. acetivorans dimeric protoglobin shows a selectivity ratio for O 2 /CO binding to the haem that favours O 2 ligation and anticooperativity in ligand binding. Both properties are exceptional within the Hb superfamily.
⁎Among heme-based sensors, recent phylogenomic and sequence analyses have identified 34 globin coupled sensors (GCS), to which an aerotactic or gene-regulating function has been tentatively ascribed. Here, the structural and biochemical characterization of the globin domain of the GCS from Geobacter sulfurreducens (GsGCS 162 ) is reported. A combination of X-ray crystallography (crystal structure at 1.5 Å resolution), UV-vis and resonance Raman spectroscopy reveals the ferric GsGCS 162 as an example of bishistidyl hexa-coordinated GCS. In contrast to the known hexa-coordinated globins, the distal heme-coordination in ferric GsGCS 162 is provided by a His residue unexpectedly located at the E11 topological site. Furthermore, UV-vis and resonance Raman spectroscopy indicated that ferrous deoxygenated GsGCS 162 is a penta-/hexa-coordinated mixture, and the heme hexa-to-penta-coordination transition does not represent a rate-limiting step for carbonylation kinetics. Lastly, electron paramagnetic resonance indicates that ferrous nitrosylated GsGCS 162 is a penta-coordinated species, where the proximal HisF8-Fe bond is severed. Abbreviations used: GCS, globin-coupled sensor; GsGCS 162 , globin domain of GCS from Geobacter sulfurreducens; PAS, an acronym formed from the names of the first three proteins (the Period clock protein of Drosophila, the Aryl hydrocarbon receptor nuclear translocator of vertebrates, and the Single-minded protein of Drosophila) recognized as sharing such sensor motif; CooA, transcriptional activator of coo operons encoding proteins required to metabolize CO as a sole energy
Although essentially unknown, several functions are hypothesized for neuroglobin and cytoglobin, two new members of the globin family. In this article, we try to shed more light on their possible roles in hypoxia and detoxification of reactive oxygen species in vivo. The relative transcriptional changes of neuroglobin and cytoglobin in a situation of chronic hypoxia in mice were examined using real‐time quantitative PCR. The kinetics of the hypoxic expression of neuroglobin (brain, eyes) and cytoglobin (brain, eyes, liver, heart, skeletal muscle) is organ‐specific. Moreover, reactive oxygen species production is higher in liver than in the other tissues. In eyes, the negative correlation, after reoxygenation, between neuroglobin protein level and H2O2 concentration is a first proof of a reactive oxygen species‐scavenging function for neuroglobin. In addition, apoptotic cell death after hypoxia is for the first time demonstrated in heart and liver.
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