, Volume 92, Issue 1, pp 17-34
Date: 25 Apr 2007

Structural basis for the mechanism of electron bifurcation at the quinol oxidation site of the cytochrome bc 1 complex

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Abstract

At the heart of the Q cycle hypothesis, the cytochrome bc 1 complex (bc 1) is required to separate the two electrons from a quinol molecule at the quinol oxidation site. Recent studies have brought to light an intricate mechanism for this bifurcated electron transfer. A survey of the protein data bank shows 30 entries for the structures of bc 1 and the homologous b 6 f complex. These structures provide considerable insights into the structural organization of mitochondrial, bacterial, and plant enzymes. Crystallographic binding studies of bc 1 with either quinone reduction (QN) and/or quinol oxidation (QP) site inhibitors offer atomic details on how these compounds interact with residues at their respective sites. Most importantly, the different locations and apparent flexibility observed in crystals for the extrinsic domain of the iron-sulfur protein (ISP) subunit suggest a mechanism for electron bifurcation at the QP site. Analyses of various inhibitor-bound structures revealed two classes of QP site inhibitors: Pm inhibitors that promote ISP mobility and Pf inhibitors that favor the fixation of the ISP conformation. Those analyses also shed light on a possible process by which the ISP motion switch is controlled. The first phase reduction of ISP is shown to be comparable to the reduction of the b L heme by pre-steady state kinetic analysis, whereas the second phase reduction of ISP share similar kinetics with the reduction of the b H heme. The reduction of cyt c 1 is measured much slower, indicating that the reduced ISP remains bound at the QP site until the reduced heme b L is oxidized by the heme b H and supporting the existence of a control mechanism for the ISP motion switch.