Mutations at the Q_o Site of the Cytochrome bc₁ Complex Strongly Affect Oxygen Binding

The homodimeric bc₁ protein complex is embedded in membranes of mitochondria and photosynthetic bacteria, where it transports protons across the membrane to maintain an electrostatic potential used to drive ATP synthesis as part of the respiratory or photosynthetic pathways. The reaction cycle of the bc₁ complex is driven by series of redox processes involving substrate molecules from the membrane, but occasional side reactions between an intermediate semiquinone substrate and molecular oxygen are suspected to be a source of toxic superoxide, which is believed to be a factor in aging. The present investigation employs molecular dynamics simulations to study the effect of mutations in the Q_o binding sites of the bc₁ complex on the ability of oxygen molecules to migrate to and bind at various locations within the complex. It is found that the mutations strongly affect the ability of oxygen to bind at the Q_o sites, and moreover, different behavior of the two monomers of the bc₁ complex is observed. The conformational differences at the Q_o sites of the two monomers are studied in detail and discussed. The anionic form of semiquinone was identified as leading to the greatest opportunity for side reactions with oxygen.