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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 (Berry et al. 2013). 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). 

As much as two-thirds of the proton gradient used for transmembrane free energy storage in oxygenic photosynthesis is generated by the cytochrome b6f complex. The proton uptake pathway from the electrochemically negative (n) aqueous phase to the n-side quinone binding site of the complex, and a probable route for proton exit to the positive phase resulting from quinol oxidation, are defined in a 2.70-A crystal structure and in structures with quinone analog inhibitors at 3.07 A (tridecyl- stigmatellin) and 3.25-A (2-nonyl-4-hydroxyquinoline N-oxide) resolution (Hasan et al. 2013). The simplest n-side proton pathway extends from the aqueous phase via Asp20 and Arg207 (cytochrome b6 subunit) to quinone bound axially to heme c(n). On the positive side, the heme-proximal Glu78 (subunit IV), which accepts protons from plastosemiquinone, defines a route for H+ transfer to the aqueous phase. These pathways provide a structure-based description of the quinone-mediated proton transfer responsible for generation of the transmembrane electrochemical potential gradient in oxygenic photosynthesis.

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 Qo site to generate a reactive semiquinone which reduces a low potential cytochrome b heme (bL). bL quickly transfers an electron to the high potential cytochrome b (bH) located on the opposite side of the membrane. Reduced bH is then oxidized by a quinone or semiquinone at the Qi site. Proton release thus probably occurs as a result of both proton translocation and QH2 deprotonation at the Qo site coupled to protonation of the reduced Q at the Qi site. Both Qi and Qo are probably localized to the cytochrome b protein. The possible H+ translocation pathways and mechanisms have been reviewed by Schultz and Chan (2001).

The bifurcated electron transfer reaction, which is built into this mechanism, recycles one electron, thus allowing it to translocate two protons per one electron moving to the high-potential redox chain. Smirnov and Nori (2012) studied the Q-cycle mechanism in an artificial system that mimics the bf complex of plants and cyanobacteria in the regime of ferredoxin-dependent cyclic electron flow. They described a time sequence of electron and proton transfer reactions in the complex, finding energetic conditions when the bifurcation of the electron pathways at the positive side of the membrane occurs naturally, without additional gates. They showed that this system is able to translocate 1.8 protons, on average, per one electron, with a thermodynamic efficiency of ~32% or higher (Smirnov and Nori, 2012).

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 cytochrome bc1 complexes have been reviewed from structure, function and mechanistic aspects (Xia et al. 2012).

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

quinol (QH2) + 2 cytochrome c (ox) + 2H+ (in) → quinone (Q) + 2 cytochrom2012) studied the Q-cycle mechanism in an artificial system that mimics the bf complex of plants and cyanobacteria in the regime of ferredoxin-dependent cyclic electron flow. They described a time sequence of electron and proton transfer reactions in the complex, finding energetic conditions when the bifurcation of the electron pathways at the positive side of the membrane occurs naturally, without additional gates. They showed that this system is able to translocate 1.8 protons, on average, per one electron, with a thermodynamic efficiency of ~32% or higher (Smirnov and Nori, 2012).

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 cytochrome bc1 complexes have been reviewed from structure, function and mechanistic aspects (Xia et al. 2012).

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).

 

References associated with 3.D.3 family:

Berry, E.A., H. De Bari, and L.S. Huang. (2013). Unanswered questions about the structure of cytochrome bc1 complexes. Biochim. Biophys. Acta. 1827: 1258-1277. 23624176
Brandt, U. and B. Trumpower. (1994). The protonmotive Q cycle in mitochondria and bacteria. Crit. Rev. Biochem. Mol. Biol. 29: 165-197. 8070276
Dudkina, N.V., H. Eubel, W. Keegstra, E.J. Boekema, and H.P. Braun. (2005). Structure of a mitochondrial supercomplex formed by respiratory-chain complexes I and III. Proc. Natl. Acad. Sci. USA 102: 3225-3229. 15713802
Hasan, S.S., E. Yamashita, D. Baniulis, and W.A. Cramer. (2013). Quinone-dependent proton transfer pathways in the photosynthetic cytochrome b6f complex. Proc. Natl. Acad. Sci. USA 110: 4297-4302. 23440205
Iwata, S., J.W. Lee, K. Okada, J.K. Lee, M. Iwata, B. Rasmussen, T.A. Link, S. Ramaswamy, and B.K. Jap. (1998). Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science 281: 64-71. 9651245
Kurisu, G., H. Zhang, J.L. Smith, and W.A. Cramer. (2003). Structure of the cytochrome b6f complex of oxygenic photosynthesis: tuning the cavity. Science 302: 1009-1014. 14526088
Schultz, B.E. and S.I. Chan. (2001). Structures and proton-pumping strategies of mitochondrial respiratory enzymes. Annu. Rev. Biophys. Biomol. Struct. 30: 23-65. 11340051
Smirnov, A.Y. and F. Nori. (2012). Modeling the Q-cycle mechanism of transmembrane energy conversion. Phys Biol 9: 016011. 22313690
Trumpower, B.L. (1990). Cytochrome bc1 complex of microorganisms. Microbiol. Rev. 54: 101-129. 2163487
Xia, D., C.-A. Yu, H. Kim, J.-Z. Xia, A.M. Kachurin, L. Zhang, L. Yu, and J. Deisenhofer. (1997). Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria. Science 277: 60-66. 9204897
Xia, D., L. Esser, W.K. Tang, F. Zhou, Y. Zhou, L. Yu, and C.A. Yu. (2012). Structural analysis of cytochrome bc1 complexes: implications to the mechanism of function. Biochim. Biophys. Acta. 1827: 1278-1294. 23201476
Yu, C-A., J-Z. Xia, A.M. Kachurin, L. Yu, D. Xia, H. Kim, and J. Deisenhofer. (1996). Crystallization and preliminary structure of beef heart mitochondrial cytochrome-bc1 complex. Biochim. Biophys. Acta 1275: 47-53. 8688450