Identification of Ubiquinol Binding Motifs at the Q_<i>o</i>‑Site of the Cytochrome <i>bc</i>₁ Complex

Enzymes of the <i>bc</i>₁ complex family power the biosphere through their central role in respiration and photosynthesis. These enzymes couple the oxidation of quinol molecules by cytochrome <i>c</i> to the transfer of protons across the membrane, to generate a proton-motive force that drives ATP synthesis. Key for the function of the <i>bc</i>₁ complex is the initial redox process that involves a bifurcated electron transfer in which the two electrons from a quinol substrate are passed to different electron acceptors in the <i>bc</i>₁ complex. The electron transfer is coupled to proton transfer. The overall mechanism of quinol oxidation by the <i>bc</i>₁ complex is well enough characterized to allow exploration at the atomistic level, but details are still highly controversial. The controversy stems from the uncertain binding motifs of quinol at the so-called Q_<i>o</i> active site of the <i>bc</i>₁ complex. Here we employ a combination of classical all atom molecular dynamics and quantum chemical calculations to reveal the binding modes of quinol at the Q_<i>o</i>-site of the <i>bc</i>₁ complex from <i>Rhodobacter capsulatus</i>. The calculations suggest a novel configuration of amino acid residues responsible for quinol binding and support a mechanism for proton-coupled electron transfer from quinol to iron–sulfur cluster through a bridging hydrogen bond from histidine that stabilizes the reaction complex