title: X-ray structure of the dimeric cytochrome bc(1) complex from the soil bacterium Paracoccus denitrificans at 2.7-Å resolution.
abstract: The respiratory cytochrome bc(1) complex is a fundamental enzyme in biological energy conversion. It couples electron transfer from ubiquinol to cytochrome c with generation of proton motive force which fuels ATP synthesis. The complex from the α-proteobacterium Paracoccus denitrificans, a model for the medically relevant mitochondrial complexes, lacked structural characterization. We show by LILBID mass spectrometry that truncation of the organism-specific, acidic N-terminus of cytochrome c(1) changes the oligomerization state of the enzyme to a dimer. The fully functional complex was crystallized and the X-ray structure determined at 2.7-Å resolution. It has high structural homology to mitochondrial complexes and to the Rhodobacter sphaeroides complex especially for subunits cytochrome b and ISP. Species-specific binding of the inhibitor stigmatellin is noteworthy. Interestingly, cytochrome c(1) shows structural differences to the mitochondrial and even between the two Rhodobacteraceae complexes. The structural diversity in the cytochrome c(1) surface facing the ISP domain indicates low structural constraints on that surface for formation of a productive electron transfer complex. A similar position of the acidic N-terminal domains of cytochrome c(1) and yeast subunit QCR6p is suggested in support of a similar function. A model of the electron transfer complex with membrane-anchored cytochrome c(552), the natural substrate, shows that it can adopt the same orientation as the soluble substrate in the yeast complex. The full structural integrity of the P. denitrificans variant underpins previous mechanistic studies on intermonomer electron transfer and paves the way for using this model system to address open questions of structure/function relationships and inhibitor binding.
authors: Institute for Biochemistry and Molecular Biology, ZMBZ, BIOSS Centre for Biological Signalling Studies, Stefan-Meier-Strasse 17, Albert-Ludwigs-University, 79104 Freiburg, Germany. thomas.kleinschroth@biochemie.uni-freiburg.de
authors: Thomas
authors: T
authors: Kleinschroth
authors: Michela
authors: M
authors: Castellani
authors: Chi H
authors: CH
authors: Trinh
authors: Nina
authors: N
authors: Morgner
authors: Bernhard
authors: B
authors: Brutschy
authors: Bernd
authors: B
authors: Ludwig
authors: Carola
authors: C
authors: Hunte
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D045222:Electron Transport Chain Complex Proteins / Q000737:chemistry; D014450:Electron Transport Complex III / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010231:Paracoccus denitrificans / Q000201:enzymology*; D011090:Polyenes / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D012988:Soil Microbiology
chemical_list: D000900:Anti-Bacterial Agents; D045222:Electron Transport Chain Complex Proteins; D011090:Polyenes; D021122:Protein Subunits; C037989:Rieske iron-sulfur protein; C041573:stigmatellin; D014450:Electron Transport Complex III