Structural basis for energy transduction by respiratory alternative complex III

Joana S Sousa,Patrícia N Refojo,Janet Vonck,Miguel Teixeira,Filipa Calisto,Julian D Langer,Werner Kühlbrandt,Manuela M Pereira,Deryck J Mills

doi:10.1038/s41467-018-04141-8

Abstract

Electron transfer in respiratory chains generates the electrochemical potential that serves as energy source for the cell. Prokaryotes can use a wide range of electron donors and acceptors and may have alternative complexes performing the same catalytic reactions as the mitochondrial complexes. This is the case for the alternative complex III (ACIII), a quinol:cytochrome c/HiPIP oxidoreductase. In order to understand the catalytic mechanism of this respiratory enzyme, we determined the structure of ACIII from Rhodothermus marinus at 3.9 Å resolution by single-particle cryo-electron microscopy. ACIII presents a so-far unique structure, for which we establish the arrangement of the cofactors (four iron–sulfur clusters and six c-type hemes) and propose the location of the quinol-binding site and the presence of two putative proton pathways in the membrane. Altogether, this structure provides insights into a mechanism for energy transduction and introduces ACIII as a redox-driven proton pump.

Highlights

Electron transfer in respiratory chains generates the electrochemical potential that serves as energy source for the cell
The reaction was thought to be exclusively catalyzed by the bc1/b6f complex[2], known as complex III. This notion changed with the identification of alternative complex III (ACIII), a quinol:cytochrome c/high potential iron–sulfur protein (HiPIP) oxidoreductase that was identified in Rhodothermus marinus[3]
Their expression in these may depend on the cellular metabolic needs, as it has been reported for respiratory enzymes performing the same catalytic activity, such as complex I and NDH-2 in Escherichia coli[9]

Summary

Introduction

Electron transfer in respiratory chains generates the electrochemical potential that serves as energy source for the cell. Prokaryotes can use a wide range of electron donors and acceptors and may have alternative complexes performing the same catalytic reactions as the mitochondrial complexes. This is the case for the alternative complex III (ACIII), a quinol:cytochrome c/HiPIP oxidoreductase. ACIII presents a so-far unique structure, for which we establish the arrangement of the cofactors (four iron–sulfur clusters and six c-type hemes) and propose the location of the quinol-binding site and the presence of two putative proton pathways in the membrane. The reaction was thought to be exclusively catalyzed by the bc1/b6f complex[2], known as complex III This notion changed with the identification of alternative complex III (ACIII), a quinol:cytochrome c/high potential iron–sulfur protein (HiPIP) oxidoreductase that was identified in Rhodothermus marinus[3]. Our structure shows that ACIII meets all requirements for an energy-transducing machine that couples quinol oxidation to translocation of protons across the membrane

Methods

Results

Conclusion