Lipid binding to cytoglobin leads to a change in heme coordination: a role for cytoglobin in lipid signalling of oxidative stress
Résumé
Cytoglobin is a recently discovered hexacoordinate hemoglobin that does not appear to function as a classical oxygen binding protein. Its function is unknown and studies on the effects of changes in its expression have not decisively determined its role within the cell. We report that the protein is transformed from hexacoordinate to pentacoordinate on binding a lipid molecule. This transformation occurs with the ferric oxidation state of the protein, but not the ferrous state, indicating that this process only occurs under an oxidative environment and may thus be related to redox-liked cell signaling mechanisms. Oleate binds to the protein in a 1:1 stoichiometry and with high affinity (KD= 0.7 μM), however stopped-flow kinetic measurements yield a KD value of 110 μM. The discrepancy between these KD values may be rationalized by recognizing that cytoglobin is a disulfide linked dimer and invoking cooperativity in oleate binding. The lipid-induced transformation of cytoglobin from hexacoordinate to pentacoordinate does not occur with similar hexacoordinate hemoglobins such as neuroglobin, and therefore appears to be a unique property of cytoglobin amongst the hemoglobin superfamily. The lipid-derived transformation may explain why cytoglobin has enhanced peroxidatic activity, converting lipids to various oxidized products, a property virtually absent from neuroglobin and much decreased in myoglobin. We propose that the binding of ferric cytoglobin to lipids and their subsequent transformation may be integral to the physiological function of cytoglobin, generating cell signaling lipid molecules under an oxidative environment.
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