Regulation of Cytoglobin‐lipid Interactions by Surface Mutations

Cytoglobin is a heme protein of the globin family. Despite sequence homology with hemoglobin and myoglobin, cytoglobin shows a different heme coordination pattern. Instead of the single histidine, pentacoordinated heme iron of hemoglobin and myoglobin, cytoglobin shows bis‐histidine, hexacoordinate heme iron ligation. This is similar to the behavior observed in the related protein neuroglobin. Although conserved in most vertebrates, the function of cytoglobin is yet unknown. The changes in heme coordination lead to properties not consistent with an oxygen transport role, and a number of functions such as scavenging of reactive oxygen species, nitrite reduction, and nitric oxide dioxygenation have been proposed. In previous work, we have shown that cytoglobin has an intrinsic peroxidase activity that can be modulated by lipids and by the oxidation of two surface cysteines, suggesting a role of cytoglobin regulated by oxidative stress. We have proposed a model for lipid binding based on computational studies, highlighting several cytoglobin residues that can modulate the protein‐lipid interactions. Here we studied the lipid binding properties of several cytoglobin mutations selected from our previous models.