Domain conformational switch of the iron-sulfur protein in cytochrome bc1 complex is induced by the electron transfer from cytochrome bL to bH

Intensive biochemical, biophysical and structural studies of the cytochrome (cyt) bc1 complex in the past have led to the formulation of the “protonmotive Q-cycle” mechanism for electron and proton transfer in this vitally important complex. The key step of this mechanism is the separation of electrons during the oxidation of a substrate quinol at the QP site with both electrons transferred simultaneously to ISP and cyt bL when the extrinsic domain of ISP (ISP-ED) is located at the b-position. Pre-steady state fast kinetic analysis of bc1 demonstrates that the reduced ISP-ED moves to the c1-position to reduce cyt c1 only after the reduced cyt bL is oxidized by cyt bH. However, the question of how the conformational switch of ISP-ED is initiated remains unanswered. The results obtained from analysis of inhibitory efficacy and binding affinity of two types of QP site inhibitors, Pm and Pf, under various redox states of the bc1 complex, suggest that the electron transfer from heme bL to bH is the driving force for the releasing of the reduced ISP-ED from the b-position to c1-position to reduce cyt c1.