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Structure of fumarate reductase from Wolinella succinogenes at 2.2 Å resolution

Nature volume 402, pages 377–385 (1999)Cite this article

Abstract

Fumarate reductase couples the reduction of fumarate to succinate to the oxidation of quinol to quinone, in a reaction opposite to that catalysed by the related complex II of the respiratory chain (succinate dehydrogenase). Here we describe the crystal structure at 2.2 Å resolution of the three protein subunits containing fumarate reductase from the anaerobic bacterium Wolinella succinogenes. Subunit A contains the site of fumarate reduction and a covalently bound flavin adenine dinucleotide prosthetic group. Subunit B contains three iron–sulphur centres. The menaquinol-oxidizing subunit C consists of five membrane-spanning, primarily helical segments and binds two haem b molecules. On the basis of the structure, we propose a pathway of electron transfer from the dihaem cytochrome b to the site of fumarate reduction and a mechanism of fumarate reduction. The relative orientations of the soluble and membrane-embedded subunits of succinate:quinone oxidoreductases appear to be unique.

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Figure 1: Representative parts of the experimental electron-density maps for crystal form A calculated with the MIRAS phases after density modification and phase extension to 2.2 Å resolution. C, N, O, P and S atoms are shown in grey, blue, red, light green and green, respectively; haem iron centres are shown in orange.
Figure 2: The three-dimensional structure of fumarate reductase.
Figure 3: Structure of the subunits of W. succinogenes fumarate reductase.
Figure 4: The dicarboxylate binding site in subunit A.
Figure 5: Possible mechanism of fumarate reduction in W. succinogenes fumarate reductase involving the residues shown in Fig. 4.
Figure 6: Arrangement of the prosthetic groups in the fumarate reductase dimer and possible electron-transfer pathways, including the position of bound fumarate (Fum).

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Acknowledgements

We thank A. Mattevi and co-workers for providing the coordinates of the E. coli L-aspartate oxidase before release for the Protein Data Bank; S. Gemeinhardt, O. Schürmann (both Institut für Mikrobiologie), C. Weiss, B. Marx, C. Münke, C. Wardenberg and D. Vinzenz (all at MPI Biophysik) for technical assistance; A. Thompson (EMBL Grenoble), G. Leonard and E. Mitchell (both ESRF) for support during data acquisition and preliminary data processing at ESRF Grenoble beamline BM14; and L.-O. Essen for providing purified tetrakis-(acetoxymercuri)-methane (TAMM). This work was supported by the Deutsche Forschungsgemeinschaft (SFB 472, grants to A.K. and H.M.) and the Max-Planck-Gesellschaft.

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  1. Manfred Auer

    Present address: Skirball Institute of Biomolecular Medicine, NYU Medical Center, 540 First Avenue, New York, New York, 10016, USA

Authors and Affiliations

  1. Max-Planck-Institut für Biophysik, Heinrich-Hoffmann-Strasse 7, Frankfurt am Main, D-60528, Germany

    C. Roy D. Lancaster, Manfred Auer & Hartmut Michel

  2. Johann Wolfgang Goethe-Universität, Institut für Mikrobiologie, Marie-Curie-Strasse 9, Frankfurt am Main, D-60439, Germany

    Achim Kröger

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Correspondence to C. Roy D. Lancaster or Hartmut Michel.

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Lancaster, C., Kröger, A., Auer, M. et al. Structure of fumarate reductase from Wolinella succinogenes at 2.2 Å resolution. Nature 402, 377–385 (1999). https://doi.org/10.1038/46483

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