Abstract
Proton-translocating respiratory complexes assemble into supercomplexes that are proposed to increase the efficiency of energy conversion and limit the production of harmful reactive oxygen species during aerobic cellular respiration. Cytochrome bc complexes and cytochrome aa3 oxidases are major drivers of the proton motive force that fuels ATP generation via respiration, but how wasteful electron- and proton transfer is controlled to enhance safety and efficiency in the context of supercomplexes is not known. Here, we address this question with the 2.8 Å resolution cryo-EM structure of the cytochrome bcc-aa3 (III2-IV2) supercomplex from the actinobacterium Corynebacterium glutamicum. Menaquinone, substrate mimics, lycopene, an unexpected Qc site, dioxygen, proton transfer routes, and conformational states of key protonable residues are resolved. Our results show how safe and efficient energy conversion is achieved in a respiratory supercomplex through controlled electron and proton transfer. The structure may guide the rational design of drugs against actinobacteria that cause diphtheria and tuberculosis.
Highlights
Proton-translocating respiratory complexes assemble into supercomplexes that are proposed to increase the efficiency of energy conversion and limit the production of harmful reactive oxygen species during aerobic cellular respiration
The resolved conformational states of three conserved key protonable residues and of haem a3 propionate δ provide the basis for controlled proton uptake, loading and release and for effective proton pumping in cyt c oxidases
In contrast to all other bc complexes known so far, which enable bifurcated electron transfer with a mobile Rieske protein[1,52], the homologous subunit QcrA is integrated into the supercomplex as a nonmobile subunit (Fig. 4a, b)
Summary
Proton-translocating respiratory complexes assemble into supercomplexes that are proposed to increase the efficiency of energy conversion and limit the production of harmful reactive oxygen species during aerobic cellular respiration. Cytochrome bc complexes and cytochrome aa[3] oxidases are major drivers of the proton motive force that fuels ATP generation via respiration, but how wasteful electron- and proton transfer is controlled to enhance safety and efficiency in the context of supercomplexes is not known. We address this question with the 2.8 Å resolution cryo-EM structure of the cytochrome bcc-aa[3] (III2-IV2) supercomplex from the actinobacterium Corynebacterium glutamicum. Our study may enable for metabolic engineering of medically and economically important actinobacteria[24], a highly diverse phylum that includes producers of amino acids and other natural products including clinically used antibiotics, and could foster rational drug design against pathogenic actinobacteria which cause diphtheria and tuberculosis[25]
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