Succinate: quinone oxidoreductases: new insights from X-ray crystal structures.
Membrane-bound succinate dehydrogenases (succinate:quinone reductases, SQR) and fumarate reductases (quinol:fumarate reductases, QFR) couple the oxidation of succinate to fumarate to the reduction of quinone to quinol and also catalyse the reverse reaction. SQR (respiratory complex II) is involved in aerobic metabolism as part of the citric acid cycle and of the aerobic respiratory chain. QFR is involved in anaerobic respiration with fumarate as the terminal electron acceptor, and is part of an electron transport chain catalysing the oxidation of various donor substrates by fumarate. QFR and SQR complexes are collectively referred to as succinate:quinone oxidoreductases (EC 1.3.5.1), have very similar compositions and are predicted to share similar structures. The complexes consist of two hydrophilic and one or two hydrophobic, membrane-integrated subunits. The larger hydrophilic subunit A carries covalently bound flavin adenine dinucleotide and subunit B contains three iron-sulphur centres. QFR of Wolinella succinogenes and SQR of Bacillus subtilis contain only one hydrophobic subunit (C) with two haem b groups. In contrast, SQR and QFR of Escherichia coli contain two hydrophobic subunits (C and D) which bind either one (SQR) or no haem b group (QFR). The structure of W. succinogenes QFR has been determined at 2.2 A resolution by X-ray crystallography (C.R.D. Lancaster, A. Kröger, M. Auer, H. Michel, Nature 402 (1999) 377-385). Based on this structure of the three protein subunits and the arrangement of the six prosthetic groups, a pathway of electron transfer from the quinol-oxidising dihaem cytochrome b to the site of fumarate reduction and a mechanism of fumarate reduction was proposed. The W. succinogenes QFR structure is different from that of the haem-less QFR of E. coli, described at 3.3 A resolution (T.M. Iverson, C. Luna-Chavez, G. Cecchini, D.C. Rees, Science 284 (1999) 1961-1966), mainly with respect to the structure of the membrane-embedded subunits and the relative orientations of soluble and membrane-embedded subunits. Also, similarities and differences between QFR transmembrane helix IV and transmembrane helix F of bacteriorhodopsin and their implications are discussed.
Lancaster
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CR
Max-Planck-Institut für Biophysik, Abteilung Molekulare Membranbiologie, Frankfurt am Main, Germany. lancaster@mpibp-frankfurt.mpg.de
Kröger
A
A
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004579:Electron Transport; D042963:Electron Transport Complex II; D004926:Escherichia coli; D005420:Flavoproteins / Q000737:chemistry; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism; D016968:Wolinella
D005420:Flavoproteins; D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; C424907:quinol fumarate reductase; D013385:Succinate Dehydrogenase