Thus, investigations targeting these two heme proteins in their ferric state are important to the scientific community.Īccording to studies using surface affinity-based surface plasmon resonance (SPR), nanopore-based nanopipettes, and solution-based isothermal titration calorimetry (ITC) experimental techniques, ferric human Ngb (referred to as hNgb hereafter) interacts with ferric Cyt c (referred to as Cyt c hereafter) with a micromolar affinity 12, 14, 20. Since a redox reaction between Ngb and Cyt c is not required to prevent the formation of the apoptosome, the binding of Ngb to Cyt c alone is sufficient to block the Cyt c-induced caspase 9 activation 19. During ischemic insults, the cellular apoptotic pathway is activated, leading to the release of ferric Cyt c, which is an essential component of the apoptosome, into the cytoplasm 16, 17, 18. This mitochondrial heme protein triggers cell apoptosis during apoptotic cell signaling 15. Therefore, recent studies have increasingly explored the binding partners of Ngb 9, 10, 11, 12.Ĭytochrome c (Cyt c), which is another heme protein 13, is a known Ngb binding partner 12, 14. However, the mechanism of Ngb neuroprotection is unclear 6, 7, and further studies investigating the neuroprotective role of Ngb are required 8. During hypoxic-ischemic insults, Ngb remains up-regulated and protects neurons 5. Ngb has been proposed to be involved in the regulation of Alzheimer’s disease 4. The structure of Ngb is similar to that of myoglobin 3. Neuroglobin (Ngb) is a six-coordinated heme protein that is mainly expressed in nervous and endocrine tissues 1 and the retina 2. Our computational results, together with an optimized structure of the hNgb-Cyt c complex, provide unique insights into how the hNgb-Cyt c complex can abate the apoptotic cascade without an hNgb-Cyt c redox reaction. We identified important residues involved in the complex formation, including K72 in Cyt c, which is otherwise known to interact with the apoptotic protease-activation factor-1. In this work, we used a combination of computational modeling and surface plasmon resonance experiments to obtain and characterize the complex formation between oxidized hNgb and Cyt c. However, the exact nature of the interactions between oxidized human neuroglobin (hNgb) and Cyt c is not well understood. Therefore, a detailed information on the Ngb-Cyt c interactions is important for understanding apoptosis. Binding of Ngb to Cyt c alone is sufficient to block the caspase 9 activation by ferric Cyt c that is released during ischemic insults. The formation of a complex between neuroglobin (Ngb) and cytochrome c (Cyt c) has an important biological role in preventing apoptosis.
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