An Electronic Bus Bar Lies in the Core of Cytochrome bc1

Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
Science (Impact Factor: 33.61). 07/2010; 329(5990):451-4. DOI: 10.1126/science.1190899
Source: PubMed


The ubiquinol-cytochrome c oxidoreductases, central to cellular respiration and photosynthesis, are homodimers. High symmetry has frustrated resolution of whether cross-dimer interactions are functionally important. This has resulted in a proliferation of contradictory models. Here, we duplicated and fused cytochrome b subunits, and then broke symmetry by introducing independent mutations into each monomer. Electrons moved freely within and between monomers, crossing an electron-transfer bridge between two hemes in the core of the dimer. This revealed an H-shaped electron-transfer system that distributes electrons between four quinone oxidation-reduction terminals at the corners of the dimer within the millisecond time scale of enzymatic turnover. Free and unregulated distribution of electrons acts like a molecular-scale bus bar, a design often exploited in electronics.

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Available from: Marcin Sarewicz, Dec 12, 2013
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    • "These results are fully consistent with the results of our previous kinetic experiments performed in vitro with asymmetricallymutated variants of the fusion complexes. The measurements of flash-induced electron transfer in membranes demonstrated that inter-monomer electron transfer occurs in milliseconds or less and thus is a catalytically-relevant event [12] [15]. Furthermore, the measured activities of isolated complexes confirmed the competence of inter-monomer electron transfer in supporting the multiple enzymatic turnovers [14]. "
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    ABSTRACT: Electronic connection between Qo and Qi quinone catalytic sites of dimeric cytochrome bc1 is a central feature of the energy-conserving Q cycle. While both the intra- and inter-monomer electron transfers were shown to connect the sites in the enzyme, mechanistic and physiological significance of the latter remains unclear. Here, using a series of mutated hybrid cytochrome bc1-like complexes, we show that inter-monomer electron transfer robustly sustains the function of the enzyme in vivo, even when the two subunits in a dimer come from different species. This indicates that minimal requirement for bioenergetic efficiency is to provide a chain of cofactors for uncompromised electron flux between the catalytic sites, while the details of protein scaffold are secondary.
    Biochemical and Biophysical Research Communications 08/2014; 451(2). DOI:10.1016/j.bbrc.2014.07.117 · 2.30 Impact Factor
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    • "Several hypotheses have been raised regarding this issue with respect to whether electrons are free to equilibrate or not in the ET chains of the two cyt b monomers, but the general argument is that the kinetics of the ET reactions are predominantly controlled by the thermodynamic driving forces of the cofactors and their distances from one another [54]. This view would seem to preclude aneed for any change in the binding affinity of the FeS head domain for either oxidation–reduction relevant surface, i.e. the cyt b or cyt c surfaces, as the cyt b cofactor distance does not change. "
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    ABSTRACT: Early structures of the cytochrome bc1 complex revealed heterogeneity in the position of the soluble portion of the Rieske iron sulfur protein subunit, implicating a movement of this domain during function. Subsequent biochemical and biophysical works have firmly established that the motion of this subunit acts in the capacity of a conformationally assisted electron transfer step during the already complicated catalytic mechanism described within the modified version of Peter Mitchells Q cycle. How the movement of this subunit is initiated or how the frequency of its motion is controlled as a function of other steps during the catalysis remain topics of debate within the active research communities. This review addresses the historical aspects of the discovery and description of this movement, while attempting to provide a context for the involvement conformational motion in the catalysis and efficiency of the enzyme.
    Biochimica et Biophysica Acta 07/2013; 1827(11-12). DOI:10.1016/j.bbabio.2013.07.007 · 4.66 Impact Factor
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    • "The cytochrome bc 1 complexes are functional dimers capable of electron exchange between the monomers via closely placed heme b p [32] [33] [34]. In the bc 1 -type complexes, under physiological conditions of a half-reduced ubiquinone pool, a total of two electrons seem to be continuously present in the dimeric cytochrome b moiety [33] [35], owing to a possibility of electron equilibration with the membrane quinol pool via centers N, see [1] and the references therein. "
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    ABSTRACT: This review traces the evolution of the cytochrome bc complexes from their early spread among prokaryotic lineages and up to the mitochondrial cytochrome bc1 complex (complex III) and its role in apoptosis. The results of phylogenomic analysis suggest that the bacterial cytochrome b6f-type complexes with short cytochromes b were the ancient form that preceded in evolution the cytochrome bc1-type complexes with long cytochromes b. The common ancestor of the b6f-type and the bc1-type complexes probably resembled the b6f-type complexes found in Heliobacteriaceae and in some Planctomycetes. Lateral transfers of cytochrome bc operons could account for the several instances of acquisition of different types of bacterial cytochrome bc complexes by archaea. The gradual oxygenation of the atmosphere could be the key evolutionary factor that has driven further divergence and spread of the cytochrome bc complexes. On one hand, oxygen could be used as a very efficient terminal electron acceptor. On the other hand, auto-oxidation of the components of the bc complex results in the generation of reactive oxygen species (ROS), which necessitated diverse adaptations of the b6f-type and bc1-type complexes, as well as other, functionally coupled proteins. A detailed scenario of the gradual involvement of the cardiolipin-containing mitochondrial cytochrome bc1 complex into the intrinsic apoptotic pathway is proposed, where the functioning of the complex as an apoptotic trigger is viewed as a way to accelerate the elimination of the cells with irreparably damaged, ROS-producing mitochondria. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.
    Biochimica et Biophysica Acta 07/2013; 1827(11-12). DOI:10.1016/j.bbabio.2013.07.006 · 4.66 Impact Factor
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