3.D.3 The Proton-translocating Quinol:Cytochrome c Reductase (QCR) Superfamily

Proteins of the QCR family (also known as the cytochrome bc₁ complex or the mitochondrial respiratory complex III) include three subunits in certain bacteria and eleven subunits in bovine heart mitochondria. Homologous complexes participate exclusively in respiration in eukaryotic mitochondria but participate in respiration, cyclic photosynthetic electron transfer, denitrification, and nitrogen fixation in phylogenetically diverse bacteria. In all cases, the complex transfers electrons from a quinol to cytochrome c and links electron transfer to proton translocation. There are two b cytochromes, one c₁ cytochrome, one Reiske 2Fe-2S center and a bound ubiquinone per subunit. The structure of the bovine mitochondrial complex has been solved to 2.9 Å resolution. The complex is a dimer of ten subunits per monomer. There are 13 transmembrane helices per monomer. The cytochrome b protein had been predicted to possess 8 or 9 TMSs; the cytochrome c₁ protein 1 TMS, and the Fe₂S₂ protein 1 or 2 TMSs. Most of the masses of core proteins I and II protrudes from the matrix side of the membrane whereas the cytochrome b protein is located primarily in the membrane, and most of the c₁ and iron-sulfur proteins including their redox centers are located on the cytoplasmic side of the membrane. Electron flow from ubiquinol to cytochrome c is coupled to the electrogenic extrusion of protons, probably two per electron. The sequences of all eleven proteins of the bovine enzyme complex, of the three proteins of the Paracoccus denitrificans enzyme and of several other QCRs are known. Three of the eukaryotic subunits are homologous to the three Paracoccus subunits.

The cytochrome b₆f complex of the cyanobacterium, Synechocystis PCC6803, has four subunits, two of which are equivalent to the cytochrome b subunit of Paracoccus. The high-resolution (3 Å) 3-D structure of the b₆f complex from the thermophilic cyanobacterium, Mastigocladus laminosus has been solved (Kurisu et al., 2003). This complex shuttles electrons between photosystems I and II reaction centers for oxygenic photosynthesis. It generated a pmf for ATP synthesis. The dimeric complex contains a large quinone exchange cavity where a heme is bound. The core of the b₆f complex resembles the respiratory cytochrome bc₁ complex, but the domain arrangement outside the core and the complement of prosthetic groups is strikingly different (Kurisu et al., 2003).

The Q cycle, by which a proton motive force is believed to be generated, involves two distinct quinol/quinone binding sites. Quinol is first oxidized by the Rieske Fe₂-S₂ center at the Q_o site to generate a reactive semiquinone which reduces a low potential cytochrome b heme (b_L). b_L quickly transfers an electron to the high potential cytochrome b (b_H) located on the opposite side of the membrane. Reduced b_H is then oxidized by a quinone or semiquinone at the Q_i site. Proton release thus probably occurs as a result of both proton translocation and QH₂ deprotonation at the Q_o site coupled to protonation of the reduced Q at the Q_i site. Both Q_i and Q_o are probably localized to the cytochrome b protein. The possible H⁺ translocation pathways and mechanisms have been reviewed by Schultz and Chan (2001).

The different mitochondrial complexes, I, III and IV have been shown to interact physically, and a stable supercomplex of complex I with dimeric complex III has been isolated from plants (Dudkina et al., 2005).

The overall reaction catalyzed by the protein complexes of the QCR family are:

quinol (QH₂) + 2 cytochrome c (ox) + 2H⁺ (in) → quinone (Q) + 2 cytochrome c (red) + 4H⁺ (out).

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