The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin.
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.
Hamdane
Djemel
D
Inserm U473, 94276 Le Kremlin-Bicêtre Cedex, France.
Kiger
Laurent
L
Dewilde
Sylvia
S
Green
Brian N
BN
Pesce
Alessandra
A
Uzan
Julien
J
Burmester
Thorsten
T
Hankeln
Thomas
T
Bolognesi
Martino
M
Moens
Luc
L
Marden
Michael C
MC
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
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