Neuroglobin: From structure to function in health and disease

Ascenzi, Paolo; Masi, Alessandra di; Leboffe, Loris; Fiocchetti, Marco; Nuzzo, Maria Teresa; Brunori, Maurizio; Marino, Maria

doi:10.1016/j.mam.2016.10.004

Cited by 96 publications

(153 citation statements)

References 502 publications

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“…The Ngb HP structures would then correspond to intermediate states where the gaseous ligands migrate toward the heme through the site II while no other gaseous molecules could migrate from the bulk, since both site I and the tunnel have disappeared 60 . Since we have previously shown that nitrous oxide (N 2 O) binds in site I and site II 44 , we can infer that nitrite could fit inside site II, which should not affected by structural modifications occurring during Ngb reductase activity 52 .…”

Section: Discussionmentioning

confidence: 93%

“…Moreover, this residue, together with the distal histidine and Phe 28, plays a role in the stabilization of the complex with cyanide and nitrite. It has been hypothesized that the reductase activity of Ngb would be correlated with the heme accessibility of nitrite 48–52 . In Hell’s gate globin I, a bacterial hemoglobin resembling mammalian Ngb 53 , it was shown that ligand migration is controlled by three hydrophobic residues Leu 58, Leu 99 and Tyr 123 which are structurally aligned in Ngb to three residues belonging to the mechanical nucleus, Ile 72, Leu 113 and Tyr 137.…”

Section: Discussionmentioning

confidence: 99%

“…Sites I and II are thought to define a path inside the cavity, that was proposed to store oxygen molecules on their way to the heme 7, 43 . Moreover, since the neuroprotective effects of Ngb may be mediated through several mechanisms like oxygen transport, cytochrome C reduction, nitrite reduction, interaction with G proteins, or NO scavenging activity, it has been proposed that a second ligand such as NO could be hosted in the cavity to react with the oxygen bound to the iron 25, 52, 55–59 . Site II could represent a reservoir for NO on the way to the active site.…”

Section: Discussionmentioning

confidence: 99%

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Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography

Colloc’h

Sacquin-Mora

Avella

et al. 2017

Sci Rep

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Investigating the effect of pressure sheds light on the dynamics and plasticity of proteins, intrinsically correlated to functional efficiency. Here we detail the structural response to pressure of neuroglobin (Ngb), a hexacoordinate globin likely to be involved in neuroprotection. In murine Ngb, reversible coordination is achieved by repositioning the heme more deeply into a large internal cavity, the “heme sliding mechanism”. Combining high pressure crystallography and coarse-grain simulations on wild type Ngb as well as two mutants, one (V101F) with unaffected and another (F106W) with decreased affinity for CO, we show that Ngb hinges around a rigid mechanical nucleus of five hydrophobic residues (V68, I72, V109, L113, Y137) during its conformational transition induced by gaseous ligand, that the intrinsic flexibility of the F-G loop appears essential to drive the heme sliding mechanism, and that residue Val 101 may act as a sensor of the interaction disruption between the heme and the distal histidine.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography

Colloc’h

Sacquin-Mora

Avella

et al. 2017

Sci Rep

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“…166 In particular, a high mRNA level of the gene encoding neuroglobin was found. 168 As discussed above, all of these signalling systems may be active in erythrocytes and can involve Hb. 166 The function of neuroglobin is far from clear, but it has been suggested to play a role in redox or NO regulation 167 and in regulating free sulphide levels.…”

Section: The Functions Of "New" Globinsmentioning

confidence: 98%

Regulation of erythrocyte function: Multiple evolutionary solutions for respiratory gas transport and its regulation in fish

2019

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Gas transport concepts in vertebrates have naturally been formulated based on human blood. However, the first vertebrates were aquatic, and fish and tetrapods diverged hundreds of millions years ago. Water-breathing vertebrates live in an environment with low and variable O 2 levels, making environmental O 2 an important evolutionary selection pressure in fishes, and various features of their gas transport differ from humans. Erythrocyte function in fish is of current interest, because current environmental changes affect gas transport, and because especially zebrafish is used as a model in biomedical studies, making it important to understand the differences in gas transport between fish and mammals to be able to carry out meaningful studies. Of the close to thirty thousand fish species, teleosts are the most species-numerous group.However, two additional radiations are discussed: agnathans and elasmobranchs.The gas transport by elasmobranchs may be closest to the ancestors of tetrapods. The major difference in their haemoglobin (Hb) function to humans is their high urea tolerance. Agnathans differ from other vertebrates by having Hbs, where cooperativity is achieved by monomer-oligomer equilibria. Their erythrocytes also lack the anion exchange pathway with profound effects on CO 2 transport. Teleosts are characterized by highly pH sensitive Hbs, which can fail to become fully O 2 -saturated at low pH. An adrenergically stimulated Na + /H + exchanger has evolved in their erythrocyte membrane, and plasma-accessible carbonic anhydrase can be differentially distributed among their tissues. Together, and differing from other vertebrates, these features can maximize O 2 unloading in muscle while ensuring O 2 loading in gills. K E Y W O R D Sadrenergically stimulated Na + /H + exchange, anion exchange, Bohr effect, carbonic anhydrase, erythrocyte, oxygen equilibrium curve (OEC), Root effect 2 of 16 | NIKINMAA et Al.3 40 ) stabilize the T-state (these so-called allosteric effectors bind to sites other than the O 2 binding site). The overall OEC of Hb molecules is determined by the probabilities of T-or R-state occurrence; the equilibrium between T-and R-states is virtually instantaneous.F I G U R E 4 O 2 equilibrium curves of rainbow trout (A) at resting plasma pH (7.65) and (B) at pH 7.40, where the Root effect has been induced (ie, O 2 saturation approaches asymptotically a value below full saturation, in this case maximal O 2 saturation is 69%, ie, Root effect 31%; data from 98 )

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“…The physiological role of Ngb is still elusive. Currently, it is assumed that Ngb is an endogenous neuroprotective protein, active against several brain injuries, including hypoxia, ischemia, toxicity, and oxygen/nutrient deprivation [43]. In vitro studies showed that H 2 S bound very tightly to the heme group of human ferric Ngb (MetNgb).…”

Section: Interactions Of Neuroglobin With Hydrogen Sulfidementioning

confidence: 99%

The Role of Hemoproteins: Hemoglobin, Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes

Bilska‐Wilkosz

Iciek

Górny

et al. 2017

IJMS

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Thiosulfate formation and biodegradation processes link aerobic and anaerobic metabolism of cysteine. In these reactions, sulfite formed from thiosulfate is oxidized to sulfate while hydrogen sulfide is transformed into thiosulfate. These processes occurring mostly in mitochondria are described as a canonical hydrogen sulfide oxidation pathway. In this review, we discuss the current state of knowledge on the interactions between hydrogen sulfide and hemoglobin, myoglobin and neuroglobin and postulate that thiosulfate is a metabolically important product of this processes. Hydrogen sulfide oxidation by ferric hemoglobin, myoglobin and neuroglobin has been defined as a non-canonical hydrogen sulfide oxidation pathway. Until recently, it appeared that the goal of thiosulfate production was to delay irreversible oxidation of hydrogen sulfide to sulfate excreted in urine; while thiosulfate itself was only an intermediate, transient metabolite on the hydrogen sulfide oxidation pathway. In the light of data presented in this paper, it seems that thiosulfate is a molecule that plays a prominent role in the human body. Thus, we hope that all these findings will encourage further studies on the role of hemoproteins in the formation of this undoubtedly fascinating molecule and on the mechanisms responsible for its biological activity in the human body.

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Neuroglobin: From structure to function in health and disease

Cited by 96 publications

References 502 publications

Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography

Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography

Regulation of erythrocyte function: Multiple evolutionary solutions for respiratory gas transport and its regulation in fish

The Role of Hemoproteins: Hemoglobin, Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes

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