A structural analysis of the transient interaction between the cytochrome bc(1) complex and its substrate cytochrome c

Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, D-60438 Frankfurt am Main, Germany.
Biochemical Society Transactions (Impact Factor: 3.19). 11/2008; 36(Pt 5):981-5. DOI: 10.1042/BST0360981
Source: PubMed


In cellular respiration, cytochrome c transfers electrons from the cytochrome bc1 complex to cytochrome c oxidase by transiently binding to the membrane proteins. The first X-ray structure of the yeast cytochrome bc1 complex with bound cytochrome c revealed the general architecture of the electron-transfer complex. The interface of the complex is small. The haem moieties are centrally located in a mainly non-polar contact site, which includes a cation-pi interaction and is surrounded by complementary charged residues. Only one cytochrome c1-docking site of the dimeric complex is occupied with cytochrome c. The recent 1.9 A (1 A=0.1 nm) resolution structure of the complex showed that the interface is highly hydrated. With cytochrome c bound, a higher number of interfacial water molecules are present on the cytochrome c1 interface, whereas its protein surface is not affected. Remarkably, the dimer structure is slightly asymmetric. Univalent cytochrome c binding coincides with conformational changes of the Rieske head domain and subunit QCR6p. Pronounced hydration and a mobility mismatch at the interface with disordered charged residues on the cytochrome c side are favourable for transient binding. Comparison with a new structure of the complex with bound isoform-2 cytochrome c led to the definition of a core interface, which refers to four common interaction pairs including the cation-pi interaction. They encircle the haem groups and are surrounded by variable interactions. The core interface may be a feature to gain specificity for formation of the reactive complex. The consistency in the binding interaction despite differences in primary sequence, redox state and crystal contacts, together with crystallization at physiological ionic strength, clearly suggest that the structures show the native bound state of the electron-transfer complex.

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    • "In this stretch no basic residue is found, thus showing a high analogy to the acidic domain of Qcr6p from yeast or the hinge protein from bovine heart, suggesting a similar function. For the eukaryotic counterparts a role in cytochrome c interaction was proposed [9] [10] [11] [12] [13] [14] [15] [16]. In addition these acidic domains of yeast and P. denitrificans complex III (on the Qcr6p and on the cytochrome c 1 , resp.) are expected at exactly the same position in the X-ray structures of the respective complexes 1 . "
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    ABSTRACT: The cytochrome bc(1) complex is a key component in several respiratory pathways. One of the characteristics of the eukaryotic complex is the presence of a small acidic subunit, which is thought to guide the interaction of the complex with its electron acceptor and facilitate electron transfer. Paracoccus denitrificans represents the only example of a prokaryotic organism in which a highly acidic domain is covalently fused to the cytochrome c(1) subunit. In this work, a deletion variant lacking this acidic domain has been produced and purified by affinity chromatography. The complex is fully intact as shown by its X-ray structure, and is a dimer (Kleinschroth et al., subm.) compared to the tetrameric (dimer-of-dimer) state of the wild-type. The variant complex is studied by steady-state kinetics and flash photolysis, showing wild type turnover and a virtually identical interaction with its substrate cytochrome c(552).
    Full-text · Article · Aug 2011 · Biochimica et Biophysica Acta

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    ABSTRACT: This review focuses on the terminal part of the respiratory chain where, macroscopically speaking, electron transfer (ET) switches from the two-electron donor, ubiquinol, to the single-electron carrier, cytochrome c, to finally reduce the four-electron acceptor dioxygen. With 3-D structures of prominent representatives of such multi-subunit membrane complexes known for some time, this section of the ET chain still leaves a number of key questions unanswered. The two relevant enzymes, ubiquinol:cytochrome c oxidoreductase and cytochrome c oxidase, appear as rather diverse modules, differing largely in their design for substrate interaction, internal ET, and moreover, in their mechanisms of energy transduction. While the canonical mitochondrial complexes have been investigated for almost five decades, the corresponding bacterial enzymes have been established only recently as attractive model systems to address basic reactions in ET and energy transduction. Lacking the intricate coding background and mitochondrial assembly pathways, bacterial respiratory enzymes typically offer a much simpler subunit composition, while maintaining all fundamental functions established for their complex "relatives". Moreover, related issues ranging from primary steps in cofactor insertion to supramolecular architecture of ET complexes, can also be favourably addressed in prokaryotic systems to hone our views on prototypic structures and mechanisms common to all family members.
    Preview · Article · Apr 2009 · Biochimica et Biophysica Acta
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