title: The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin.
abstract: Neuroglobin and cytoglobin reversibly bind oxygen in competition with the distal histidine, and the observed oxygen affinity therefore depends on the properties of both ligands. In the absence of an external ligand, the iron atom of these globins is hexacoordinated. There are three cysteine residues in human neuroglobin; those at positions CD7 and D5 are sufficiently close to form an internal disulfide bond. Both cysteine residues in cytoglobin, although localized in other positions than in human neuroglobin, may form a disulfide bond as well. The existence and position of these disulfide bonds was demonstrated by mass spectrometry and thiol accessibility studies. Mutation of the cysteines involved, or the use of reducing agents to break the S-S bond, led to a decrease in the observed oxygen affinity of human neuroglobin by an order of magnitude. The critical parameter is the histidine dissociation rate, which changes by about a factor of 10. The same effect is observed with human cytoglobin, although to a much lesser extent (less than a factor of 2). These results suggest a novel mechanism for the regulation of oxygen binding; contact with an appropriate electron donor would provoke the release of oxygen. Hence the oxygen affinity would be directly linked to the redox state of the cell.
authors.affiliation: Inserm U473, 94276 Le Kremlin-Bicêtre Cedex, France.
authors.forename: Djemel
authors.initials: D
authors.lastname: Hamdane
authors.forename: Laurent
authors.initials: L
authors.lastname: Kiger
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dewilde
authors.forename: Brian N
authors.initials: BN
authors.lastname: Green
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pesce
authors.forename: Julien
authors.initials: J
authors.lastname: Uzan
authors.forename: Thorsten
authors.initials: T
authors.lastname: Burmester
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankeln
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
authors.forename: Luc
authors.initials: L
authors.lastname: Moens
authors.forename: Michael C
authors.initials: MC
authors.lastname: Marden
mesh_terms: D003545:Cysteine / Q000737:chemistry; D000078842:Cytoglobin; D004220:Disulfides; D005914:Globins / Q000737:chemistry / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D000078787:Neuroglobin; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C000627265:CYGB protein, human; D000078842:Cytoglobin; D004220:Disulfides; D008024:Ligands; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D011994:Recombinant Proteins; D006639:Histidine; D005914:Globins; D003545:Cysteine; D010100:Oxygen