Abstract
Neuroglobin (Ngb), the third member of the globin family, was discovered in human and murine brains in 2000. This monomeric globin is structurally similar to myoglobin (Mb) and hemoglobin (Hb) α and β subunits, but it hosts a bis-histidyl six-coordinated heme-Fe atom. Therefore, the heme-based reactivity of Ngb is modulated by the dissociation of the distal HisE7-heme-Fe bond, which reflects in turn the redox state of the cell. The high Ngb levels (~100–200 μM) present in the retinal ganglion cell layer and in the optic nerve facilitate the O2 buffer and delivery. In contrast, the very low levels of Ngb (~1 μM) in most tissues and organs support (pseudo-)enzymatic properties including NO/O2 metabolism, peroxynitrite and free radical scavenging, nitrite, hydroxylamine, hydrogen sulfide reduction, and the nitration of aromatic compounds. Here, structural and (pseudo-)enzymatic properties of Ngb, which are at the root of tissue and organ protection, are reviewed, envisaging a possible role in the protection from neuronal degeneration of the retina and the optic nerve.
Highlights
Mammalian tetrameric hemoglobin (Hb) and monomeric myoglobin (Mb) are generally taken as macromolecular models, having been among the first proteins that were characterized from the structural and functional viewpoints
All α-helical globins are expressed in all living organisms, with putative globin genes occurring in many prokaryotes and eukaryotes
Several studies in Ngb-null mice reported that Ngb expression in the central nervous system and in the retina, rather than diffuse, is restricted to specific brain regions and to two out of the ten layers forming the retina [149,169]
Summary
Mammalian tetrameric hemoglobin (Hb) and monomeric myoglobin (Mb) are generally taken as macromolecular models, having been among the first proteins that were characterized from the structural and functional viewpoints. Adgb, Cygb, Hb, Mb, and Ngb are expressed in canonical and non-canonical sites fulfilling organ-specific (un)common functions [13]. The most striking differences between the 2/2 and the 3/3 globin folds are: (i) the drastically shortened or absent A-helix, (ii) the alteration of the C-E region, and (iii) the presence of a long polypeptide segment, which precedes the short α-helix F where the proximal HisF8 residue is located coordinating the heme-Fe atom [2,4,7,8,21]. The structural and (pseudo-)enzymatic properties of multifaced Ngb along with the possible protective role in the retina and the optic nerve are reviewed [13,42,43,44,45,46,47,48,49]
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