| Cytochrome bc1 complex, also known as complex III of the respiratory chain, is a multi-subunit protein complex embedded in the mitochondrial inner membrane and plasma membranes of many aerobic or photosynthetic bacteria. It contains three redox subunits: cytochrome b, cytochrome c1 and a so-called "Rieske protein" that contains an iron-sulfur cluster. The complex transfers electrons from ubiquinol to cytochrome c and uses the free energy thus released to generate an electro-chemical gradient across the mitochondrial inner membrane that is further utilized in ATP synthesis. The bc1 complex works through a modified "protonmotive Q-cycle" mechanism, which requires the complex to have two separate quinone-binding sites: a quinone oxidation site (Qo site) and a quinone reduction site (Qi site).;Intact bc1 complex was isolated from chicken heart mitochondria and crystallized in space group P21212 1 with cell dimensions of a = 170 A, b = 180 A, c = 240 A. Three-dimensional structures were determined to 3.0 A resolution for native bc1 complex using the Multiple Isomorphous Replacement (MIR) technique. Molecular Replacement (MR) techniques were used to determine the structures of bc1 complex treated with various inhibitors. Ubiquinone and inhibitor molecules were observed at the two quinone-binding sites in these structures. A comparison of the structures in the presence and absence of the inhibitor stigmatellin reveals two different locations for the extrinsic domain of subunit Rieske protein. This suggests a novel mechanism for electron transfer through domain movement. Significant conformational changes on the protein residues close to the quinone binding sites were also observed. Based on these observations, a model for the mechanism of bc1 complex is proposed. |
