Structure and Function in the bc1-Complex of Rhodobacter Sphaeroides

Crofts, Antony R.; Barquera, Blanca; Bechmann, Georg; Guergova, Mariana; Salcedo‐Hernández, Rubén; Hacker, Beth M.; Hong, Sung Il; Gennis, Robert B.

doi:10.1007/978-94-009-0173-5_347

Cited by 24 publications

(39 citation statements)

References 22 publications

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“…First of all, the lack of crystal structures containing quinone bound, at any redox state, in the Q o site leaves a high degree of freedom in constructing models of the binding, electron transfers, and proton release into the intermembrane space. Comparative analysis of various crystal structures containing different inhibitors of the Q o site identified the region of quinone binding consistent in amino acid composition with earlier mapping by site-directed mutagenesis (39,59). In addition, it showed displacements of polypeptide backbone in the region expected for the quinone binding (94,268).…”

Section: A Quinone Binding Q O Sitesupporting

confidence: 68%

Electronic Connection Between the Quinone and CytochromecRedox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

Sarewicz

Osyczka

2015

Physiological Reviews

137

141

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Physiol Rev 95: 219 -243, 2015; doi:10.1152/physrev.00006.2014.-Mitochondrial respiration, an important bioenergetic process, relies on operation of four membranous enzymatic complexes linked functionally by mobile, freely diffusible elements: quinone molecules in the membrane and water-soluble cytochromes c in the intermembrane space. One of the mitochondrial complexes, complex III (cytochrome bc 1 or ubiquinol: cytochrome c oxidoreductase), provides an electronic connection between these two diffusible redox pools linking in a fully reversible manner two-electron quinone oxidation/reduction with one-electron cytochrome c reduction/oxidation. Several features of this homodimeric enzyme implicate that in addition to its well-defined function of contributing to generation of proton-motive force, cytochrome bc 1 may be a physiologically important point of regulation of electron flow acting as a sensor of the redox state of mitochondria that actively responds to changes in bioenergetic conditions. These features include the following: the opposing redox reactions at quinone catalytic sites located on the opposite sides of the membrane, the inter-monomer electronic connection that functionally links four quinone binding sites of a dimer into an H-shaped electron transfer system, as well as the potential to generate superoxide and release it to the intermembrane space where it can be engaged in redox signaling pathways. Here we highlight recent advances in understanding how cytochrome bc 1 may accomplish this regulatory physiological function, what is known and remains unknown about catalytic and side reactions within the quinone binding sites and electron transfers through the cofactor chains connecting those sites with the substrate redox pools. We also discuss the developed molecular mechanisms in the context of physiology of mitochondria.

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Section: A Quinone Binding Q O Sitesupporting

confidence: 68%

Electronic Connection Between the Quinone and CytochromecRedox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

Sarewicz

Osyczka

2015

Physiological Reviews

137

141

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“…sphaeroides bc 1 complex (E295D, -G, and -Q) show an inhibited rate of quinol oxidation (ref. 30 and see Table 1), and mutants at the equivalent residue in the b 6 f complex (the related enzyme in oxygenic photosynthetic chains) are also inhibited (31). The E295G and E295Q mutants were most severely affected.…”

Section: Inhibitor and Substratementioning

confidence: 99%

Pathways for proton release during ubihydroquinone oxidation by the bc ₁ complex

Crofts

Hong

Ugulava

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

165

254

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Quinol oxidation by the bc 1 complex of Rhodobacter sphaeroides occurs from an enzyme-substrate complex formed between quinol bound at the Q o site and the iron-sulfur protein (ISP) docked at an interface on cytochrome b. From the structure of the stigmatellin-containing mitochondrial complex, we suggest that hydrogen bonds to the two quinol hydroxyl groups, from Glu-272 of cytochrome b and His-161 of the ISP, help to stabilize the enzyme-substrate complex and aid proton release. Reduction of the oxidized ISP involves H transfer from quinol. Release of the proton occurs when the acceptor chain reoxidizes the reduced ISP, after domain movement to an interface on cytochrome c 1 . Effects of mutations to the ISP that change the redox potential and͞or the pK on the oxidized form support this mechanism. Structures for the complex in the presence of inhibitors show two different orientations of Glu-272. In stigmatellin-containing crystals, the side chain points into the site, to hydrogen bond with a ring hydroxyl, while His-161 hydrogen bonds to the carbonyl group. In the native structure, or crystals containing myxothiazol or ␤-methoxyacrylate-type inhibitors, the Glu-272 side chain is rotated to point out of the site, to the surface of an external aqueous channel. Effects of mutation at this residue suggest that this group is involved in ligation of stigmatellin and quinol, but not quinone, and that the carboxylate function is essential for rapid turnover. H ؉ transfer from semiquinone to the carboxylate side chain and rotation to the position found in the myxothiazol structure provide a pathway for release of the second proton.The bc 1 complex family of enzymes plays a central role in all the main pathways of energy conversion, and the photosynthetic apparatus of Rhodobacter sphaeroides exemplifies one of the simplest of these (1-5). This system is convenient experimentally because of the ease with which electron transfer can be initiated by illumination (6). X-ray crystallographic structures of mitochondrial complexes (7-10) contain at their core the three catalytic subunits, cytochrome (cyt) b, cyt c 1 , and the Rieske iron-sulfur protein (ISP), common to the bacterial enzymes (11-13). Homology models of these show that the catalytic superstructure is highly conserved, as had been expected from studies of the mechanism, which is essentially the same in the two systems (1-5). The bc 1 complex catalyzes the oxidation of quinol and the reduction of cyt c (or c 2 ) through a modified Q cycle (1-6, 14-17). Two separate internal electron transfer chains connect three catalytic sites. At one site, heme c 1 is oxidized by cyt c 2 . Two catalytic sites in cyt b are involved in oxidation or reduction of ubiquinone. In the bifurcated reaction at the quinol-oxidizing site (the Q o site), one electron from quinol is passed to the ISP, which transfers it to cyt c 1 , while the semiquinone produced is oxidized by another chain consisting of the two b hemes of cyt b. At the quinone-reducing site (Q i -site), electrons fr...

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“…Rich et al (274) proposed a set of G values in a minimal eight-state system that provided a good fit to the data. A second mechanism (270,272,275) suggests that the b-150 form is generated by reversal of the second electron transfer of the normal forward reaction. A single equilibrium constant, calculated from the E m values for the components involved, then provided a good fit to the data.…”

Section: Mechanism Of Quinone Reduction At the Q I Sitementioning

confidence: 99%

Structure and Function of CytochromebcComplexes

Berry

Guergova-Kuras²,

Huang³

et al. 2000

Annu. Rev. Biochem.

473

461

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Key Words oxidoreductase, respiratory chain, electron transfer, crystallography, membrane protein s Abstract The cytochrome bc complexes represent a phylogenetically diverse group of complexes of electron-transferring membrane proteins, most familiarly represented by the mitochondrial and bacterial bc 1 complexes and the chloroplast and cyanobacterial b 6 f complex. All these complexes couple electron transfer to proton translocation across a closed lipid bilayer membrane, conserving the free energy released by the oxidation-reduction process in the form of an electrochemical proton gradient across the membrane. Recent exciting developments include the application of site-directed mutagenesis to define the role of conserved residues, and the emergence over the past five years of X-ray structures for several mitochondrial complexes, and for two important domains of the b 6 f complex. CONTENTS

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Structure and Function in the bc1-Complex of Rhodobacter Sphaeroides

Cited by 24 publications

References 22 publications

Electronic Connection Between the Quinone and CytochromecRedox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

Electronic Connection Between the Quinone and CytochromecRedox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

Pathways for proton release during ubihydroquinone oxidation by the bc ₁ complex

Structure and Function of CytochromebcComplexes

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Structure and Function in the bc1-Complex of Rhodobacter Sphaeroides

Cited by 24 publications

References 22 publications

Electronic Connection Between the Quinone and CytochromecRedox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

Electronic Connection Between the Quinone and CytochromecRedox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

Pathways for proton release during ubihydroquinone oxidation by the bc 1 complex

Structure and Function of CytochromebcComplexes

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Product

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Pathways for proton release during ubihydroquinone oxidation by the bc ₁ complex