Respiratory Complex III: A Bioengine with a Ligand-Triggered Electron-Tunneling Gating Mechanism.

Respiratory complex III (a.k.a., the bc 1 complex) plays a key role in the electron transport chain in aerobic cells. The bc 1 complex exhibits multiple unique electron tunneling (ET) processes, such as ET-bifurcation at the Q o site and movement of the Rieske domain. Moreover, we previously discovered that electron tunneling in the low potential arm of the bc 1 complex is regulated by a key phenylalanine residue (Phe90). The main goal of the current work is to study the dynamics of the key Phe90 residue in the electron tunneling reaction between heme b L and heme b H as a function of the occupancy of the Q o and Q i binding sites in the bc 1 complex. We simulated the molecular dynamics of four model systems of respiratory complex III with different ligands bound at the Q o and Q i binding sites. In addition, we calculated the electron tunneling rate constants between heme b L and heme b H along the simulated molecular dynamics trajectories. The binding of aromatic ligands at the Q o site induces a conformational cascade that properly positions the Phe90 residue, reducing the through-space ET distance from ∼7 to ∼5.5 Å and thus enhancing the electron transfer rate between the heme b L and the heme b H redox pair. Also, the binding of aromatic ligands at the Q i site induces conformational changes that stabilize the Phe90 conformational variation from ∼1.5 to ∼0.5 Å. Hence, our molecular dynamics simulation results show an on-demand two-step conformational connection between the occupancy of the Q o and Q i binding sites and the conformational dynamics of the Phe90 residue. Additionally, our dynamic electron tunneling results confirm our previously reported findings that the Phe90 residue acts as an electron-tunneling gate or switch, controlling the electron transfer rate between the heme b L and heme b H redox systems.