Structural highlights
Function
[NGB_MOUSE] Involved in oxygen transport in the brain. Hexacoordinate globin, displaying competitive binding of oxygen or the distal His residue to the iron atom. Not capable of penetrating cell membranes. The deoxygenated form exhibits nitrite reductase activity inhibiting cellular respiration via NO-binding to cytochrome c oxidase. Involved in neuroprotection during oxidative stress. May exert its anti-apoptotic activity by acting to reset the trigger level of mitochondrial cytochrome c release necessary to commit the cells to apoptosis.[1] [2]
Publication Abstract from PubMed
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.
Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography.,Colloc'h N, Sacquin-Mora S, Avella G, Dhaussy AC, Prange T, Vallone B, Girard E Sci Rep. 2017 May 12;7(1):1858. doi: 10.1038/s41598-017-02097-1. PMID:28500341[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Couture M, Burmester T, Hankeln T, Rousseau DL. The heme environment of mouse neuroglobin. Evidence for the presence of two conformations of the heme pocket. J Biol Chem. 2001 Sep 28;276(39):36377-82. Epub 2001 Jul 25. PMID:11473111 doi:http://dx.doi.org/10.1074/jbc.M103907200
- ↑ Dewilde S, Kiger L, Burmester T, Hankeln T, Baudin-Creuza V, Aerts T, Marden MC, Caubergs R, Moens L. Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family. J Biol Chem. 2001 Oct 19;276(42):38949-55. Epub 2001 Jul 25. PMID:11473128 doi:http://dx.doi.org/10.1074/jbc.M106438200
- ↑ Colloc'h N, Sacquin-Mora S, Avella G, Dhaussy AC, Prange T, Vallone B, Girard E. Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography. Sci Rep. 2017 May 12;7(1):1858. doi: 10.1038/s41598-017-02097-1. PMID:28500341 doi:http://dx.doi.org/10.1038/s41598-017-02097-1
