Internal Switches Modulating Electron Flow in bc1 Complex

Abstract

Ubiquinol-cytochrome c oxidoreducase (BC1) protein complex is a smart machine which employs an internal signal transduction network, regulated by the binding of natural ligands to either Qo or Qi sites, to modulate electron transfer rates between different redox pairs. Binding of natural ligands or some inhibitors leads to local conformational changes which propagate through protein and control the conformation of key residues involved in the electron tunneling pathway. Aromatic-aromatic interactions are highly utilized in this internal network since the key residues are aromatic in nature. Molecular dynamics simulations of native BC1, natural ligand and inhibitor-bound BC1 homo-dimers in membrane were performed to investigate and compare the dynamics of those key residues in their respective environments. In addition, molecular dynamics simulations reveals the transduction pathway induced by the binding of a ligand or inhibitor at their sites. Electron tunneling calculations show that there is a substantial correlated change of the electron transfer rates between different redox pairs depending on the binding of natural ligands or inhibitors.