Ubiquinone-binding proteins

Contains FMN, nonhaem Fe, acid- abile sulphur, ubiquinone-10 and lipids (Table 3.8). The several constituent polypeptides probably include ubiquinone-binding proteins (281). 

Fig. 2 Metabolism of superoxide radical and nitric oxide in the mitochondrial matrix. The numbers below the symbols indicate approximate steady state concentrations for mammalian organs under physiological conditions. The arrows reaching outside the mitochondrion indicate diffusion of HjOj and NO to the cytosol. QBP ubiquinone binding protein, NADH-DH NADH dehydrogenase...

It may be the immediate donor of electrons to a ubiquinone held by a ubiquinone-binding protein designated QP-N. In bacteria seven of these are homologs of the seven NADFl dehydrogenase subunits encoded by mtDNA (Fig. 18-3). A49-kDa subunit of complex I in fhe yeast Yarrowia lipolytica is strikingly similar to the hydrogen reactive subunit of NiFe hydrogenases (Fig. 

The polyisoprenoids dolichol (Figure 14-20 and Chapter 47) and ubiquinone (Figure 12-5) are formed from farnesyl diphosphate by the further addition of up to 16 (dolichol) or 3-7 (ubiquinone) isopentenyl diphosphate residues, respectively. Some GTP-binding proteins in the cell membrane are prenylated with farnesyl or geranylgeranyl (20 carbon) residues. Protein prenylation is believed to facilitate the anchoring of proteins into lipoid membranes and may also be involved in protein-protein interactions and membrane-associated protein trafficking. 

Schnurr et al. [22] showed that rabbit 15-LOX oxidized beef heart submitochondrial particles to form phospholipid-bound hydroperoxy- and keto-polyenoic fatty acids and induced the oxidative modification of membrane proteins. It was also found that the total oxygen uptake significantly exceeded the formation of oxygenated polyenoic acids supposedly due to the formation of hydroxyl radicals by the reaction of ubiquinone with lipid 15-LOX-derived hydroperoxides. However, it is impossible to agree with this proposal because it is known for a long time [23] that quinones cannot catalyze the formation of hydroxyl radicals by the Fenton reaction. Oxidation of intracellular unsaturated acids (for example, linoleic and arachidonic acids) by lipoxygenases can be suppressed by fatty acid binding proteins [24]. 

In both systems, membrane-bound ubiquinone plays crucial roles in the respiratory chain. Indeed, various quinones, including ubiquinone and menaquinone, are used to connect the redox reactions of various membrane proteins. In spite of the large amount of biochemical and biophysical data on quinone and quinone binding proteins, little structural... 

To begin with, the proposed ubiquinone binding site was unlike any of the previous sites that have been described in membrane proteins that bind ubiquinone. As presented above the photosynthetic reaction center (Deisenhofer etal., 1995), the bc complex (Xia etal., 1987 Zhang et al., 1998 Iwata et al., 1998 Hunte et al., 2000), and fumarate reductase (Iverson et al., 1999 Lancaster et al., 1999) bind the ubiquinone molecule within membrane-spanning helices where the ring of the ubiquinone molecule is oriented near the phospholipid head group of the membrane. Second, a large mutational study of residues at or around... 

In the h positional state , tiie distance is > 30 A between the Rieske cluster and cytochrome Cl whereas in the ci positional state , tiie Rieske [2Fe-2S] cluster is far away from tiie ubiquinone binding site and points in tiie opposite direction (Figure 3). Therefore, tiie Rieske protein has to move between these positional states in order to transfer an electron fiom ubihydroquinone to cytochrome Ci. The movement involves a rotation of the entire water soluble domain of 57 this rotation requires stretching of the flexible linker. 

Ubiquinone is a substituted (2,3-dimethoxy-5-methyl-(l,4)-)benzoquinone with a long isoprenoid side chain in position 6 (see Ref. 238). The fact that ubiquinol is a donor of two reducing equivalents, while cytochrome c is a one-electron acceptor, requires special arrangements of electron transfer (cf., the analogous but opposite problem in cytochrome oxidase). Although ubisemiquinone is very unstable in most circumstances, it can be stabilised by specific binding to a catalytic site. Two such sites have been identified in Complex III [236,239-244]. Quinone-binding proteins have also been described [194-196,245]. 

The most recent model of this membrane, the fluid mosaic model [13] is pictured in cartoon fashion in Fig. 2. In this model, the transduction proteins (complexes I-IV) are randomly dispersed in the membrane and redox equivalents are delivered from one complex to another via the mobile electron carriers cytochrome c and ubiquinone. It is necessary that cytochrome c be able to move relatively facilely from one complex to another. Thus the binding constants cannot be too high without making the associated OS rates too slow. Conversely, to prevent unproductive short circuits via cytochrome c from complex I directly to IV, there must exist molecular recognition which favors selective binding of cytochrome c to hcj and cytochrome oxidase (and perhaps disfavors binding to complex 1 or II). 

One excellent example was the recent demonstration that three ubiquinone molecules bind as co-factors to the mitochondrial membrane protein complex cytochrome bc n Two-dimensional HSQC NMR of 13C-labelled... 

Dolezal P, Likic V, Tachezy J, Lithgow T (2006) Evolution of the molecular machines for protein import into mitochondria. Science 313 314-318 Dong J-S, Lai R, Nielsen K, Fekete CA, Qiu H-F, Hinnebusch AG (2004) The essential ATP-binding cassette protein Rlil functions in translation by promoting preinitiation complex assembly. J Biol Chem 274 42157-42168 Ellis JE, Setchell KD, Kaneshiro ES (1994) Detection of ubiquinone in parasitic and free-living protozoa, including species devoid of mitochondria. Mol Biochem Parasitol 65 213-224... 

FIGURE 19-11 Cytochrome be, complex (Complex III). The complex is a dimer of identical monomers, each with 11 different subunits. (a) Structure of a monomer. The functional core is three subunits cytochrome b (green) with its two hemes (bH and foL, light red) the Rieske iron-sulfur protein (purple) with its 2Fe-2S centers (yellow) and cytochrome ci (blue) with its heme (red) (PDB ID 1BGY). (b) The dimeric functional unit. Cytochrome c, and the Rieske iron-sulfur protein project from the P surface and can interact with cytochrome c (not part of the functional complex) in the intermembrane space. The complex has two distinct binding sites for ubiquinone, QN and QP, which correspond to the sites of inhibition by two drugs that block oxidative phosphorylation. Antimycin A, which blocks electron flow from heme bH to Q, binds at QN, close to heme bH on the N (matrix) side of the membrane. Myxothiazol, which prevents electron flow from... 

QH2 to the Rieske iron-sulfur protein, binds at QP, near the 2Fe-2S center and heme bL on the P side. The dimeric structure is essential to the function of Complex III. The interface between monomers forms two pockets, each containing a QP site from one monomer and a QN site from the other. The ubiquinone intermediates move within these sheltered pockets. 

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