Abstract
AbstractDiheme-containing succinate:menaquinone oxidoreductases (Sdh) are widespread in Gram-positive bacteria but little is known about the catalytic mechanisms they employ for succinate oxidation by menaquinone. Here, we present the 2.8 Å cryo-electron microscopy structure of a Mycobacterium smegmatis Sdh, which forms a trimer. We identified the membrane-anchored SdhF as a subunit of the complex. The 3 kDa SdhF forms a single transmembrane helix and this helix plays a role in blocking the canonically proximal quinone-binding site. We also identified two distal quinone-binding sites with bound quinones. One distal binding site is formed by neighboring subunits of the complex. Our structure further reveals the electron/proton transfer pathway for succinate oxidation by menaquinone. Moreover, this study provides further structural insights into the physiological significance of a trimeric respiratory complex II. The structure of the menaquinone binding site could provide a framework for the development of Sdh-selective anti-mycobacterial drugs.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference61 articles.
1. Mitchell, P. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191, 144–148 (1961).
2. Saraste, M. Oxidative phosphorylation at the fin de siecle. Science 283, 1488–1493 (1999).
3. Iverson, T. Catalytic mechanisms of complex II enzymes: a structural perspective. Biochem. Biophys. Acta 1827, 648–657 (2013).
4. Hirsch, C. A., Rasminsky, M., Davis, B. D. & Lin, E. C. A fumarate reductase in Escherichia coli distinct from succinate dehydrogenase. J. Biol. Chem. 238, 3770–3774 (1963).
5. Hards, K., Rodriguez, S. M., Cairns, C. & Cook, G. M. Alternate quinone coupling in a new class of succinate dehydrogenase may potentiate mycobacterial respiratory control. FEBS Lett. 593, 475–486 (2019).
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