Hell's Gate globin as a model for the functionality of human neuroglobin

Abstract

Methylacidiphilum infernorum (M.infernorum) is an extremely acidophilic, aerobic, and methanotrophic bacteria in the Verrucomicrobia phylum. A unique aspect of M. Infernorum is the presence of a special globin called Hell’s Gate globin I (HGbI). This globin has a ferric heme group and the unusual ability to bind acetate as well as oxygen with a high affinity. Discovered in geothermal vents in New Zealand, the bacteria belongs to the only known group of aerobic methanotrophs outside of proteobacteria, making M. infernorum a novelty. The bacteria has acquired numerous genes, including those for enzymes of methylotrophic pathways via horizontal gene transfer, in particular, from proteobacteria. M. Infernorum is the most acidophilic bacteria capable of methane oxidation. The low pH conditions favored by M. Infernorum have interesting effects on HGbI’s ligand bonds. HGbI also facilitates fast oxygen binding and slow release due to distal residues gln and tyr. Although not everything about HGbl is known, there have been multiple functions proposed. We used these proposed functions to speculate on a structurally similar protein, human neuroglobin (Ngb). Ngb is a recently discovered protein in the human body that is found in the central nervous system. Its proposed functions include transporting oxygen, raising hypoxia tolerance, or scavenging damaging reactive oxygen/nitrogen species. Because HGbl and Ngb have been proven to be structurally similar, we compared their structures in JMol and isolated the main differences, including a shorter CD loop and the absence of a D‐helix in HGbI, and the presence of a distal Gln50(E7) in HGbI compared to the His(E7) of Ngb. We cross‐examined these differences in order to speculate on the likelihood of the previously proposed functions of both HGbI and Ngb and gain a deeper understanding of both proteins. The Mahtomedi MSOE Center for BioMolecular MAPS Team used 3‐D modeling and printing technology to examine structure‐function relationships of HGbI and Ngb. The visual model was a valuable tool in developing our story.