Redox Coupled Conformational Changes in Cytochrome BC1 Complex: Implication to the Bifurcated Electron Transfer at the Quinol Oxidation Site

Abstract

The essential respiratory chain component cytochrome bc1 complex (ubiquionol cytochrome c oxido-reductase, bc1) couples the oxidation of ubiquinol to the vectorial proton movement across the membrane, contributing to the proton motive force essential for various cellular functions. In the bc1 complex, a high potential chain, consisting of the cyt c1 and ISP subunits, and a low potential chain, made up of hemes bL and bH, converge to the quinol oxidation or QP site. By inhibitor binding coupled crystallographic studies, the extrinsic domain of the iron-sulfur protein subunit (ISP-ED) was shown to undergo a binary inhibitor-type dependent conformation switch, leading to the “surface affinity modulated ISP conformational switch” hypothesis that provides a structural basis for the electron bifurcation at the QP site essential for the Q-cycle mechanism by which the bc1 complex operates. However, how this control of ISP-ED conformational switch is achieved under non-inhibitory conditions remains obscure. Here we show by redox coupled crystallographic analysis that the conformational switch of ISP-ED is correlated strongly with the redox potential of the high potential chain. Structural changes at the ISP-ED binding sites in response to redox changes were similar to those induced by binding to the QP site with different types of inhibitors. Functional implications will be discussed.