scholarly journals Resolving Chemical Dynamics in Biological Energy Conversion: Long-Range Proton-Coupled Electron Transfer in Respiratory Complex I

2021 ◽  
Author(s):  
Ville R. I. Kaila
Keyword(s):  
Electron Transfer ◽  
Energy Conversion ◽  
Long Range ◽  
Complex I ◽  
Chemical Dynamics ◽  
Respiratory Complex ◽  
Proton Coupled Electron Transfer ◽  
Respiratory Complex I

scholarly journals Energetics and dynamics of long-range electron transfer in respiratory complex I

2018 ◽  
Vol 1859 ◽  
pp. e42
Author(s):  
Michael Röpke ◽  
Ana P. Gamiz-Hernandez ◽  
Alexander Jussupow ◽  
Mikael P. Johansson ◽  
Ville R.I. Kaila
Keyword(s):  
Electron Transfer ◽  
Long Range ◽  
Complex I ◽  
Respiratory Complex ◽  
Respiratory Complex I

scholarly journals Long-range proton-coupled electron transfer in biological energy conversion: towards mechanistic understanding of respiratory complex I

2018 ◽  
Vol 15 (141) ◽  
pp. 20170916 ◽  
Author(s):  
Ville R. I. Kaila
Keyword(s):  
Energy Conversion ◽  
Complex I ◽  
Mechanistic Model ◽  
Atomic Scale ◽  
Respiratory Complex ◽  
Proton Coupled Electron Transfer ◽  
Transduction Mechanisms ◽  
Molecular Machinery ◽  
Respiratory Complex I ◽  
Action At A Distance

Biological energy conversion is driven by efficient enzymes that capture, store and transfer protons and electrons across large distances. Recent advances in structural biology have provided atomic-scale blueprints of these types of remarkable molecular machinery, which together with biochemical, biophysical and computational experiments allow us to derive detailed energy transduction mechanisms for the first time. Here, I present one of the most intricate and least understood types of biological energy conversion machinery, the respiratory complex I, and how its redox-driven proton-pump catalyses charge transfer across approximately 300 Å distances. After discussing the functional elements of complex I, a putative mechanistic model for its action-at-a-distance effect is presented, and functional parallels are drawn to other redox- and light-driven ion pumps.

scholarly journals Functional Water Wires Catalyze Long-Range Proton Pumping in the Mammalian Respiratory Complex I

2020 ◽  
Vol 142 (52) ◽  
pp. 21758-21766
Author(s):  
Michael Röpke ◽  
Patricia Saura ◽  
Daniel Riepl ◽  
Maximilian C. Pöverlein ◽  
Ville R. I. Kaila
Keyword(s):  
Long Range ◽  
Complex I ◽  
Proton Pumping ◽  
Respiratory Complex ◽  
Respiratory Complex I

scholarly journals Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I

2017 ◽  
Vol 114 (48) ◽  
pp. 12737-12742 ◽  
Author(s):  
Justin G. Fedor ◽  
Andrew J. Y. Jones ◽  
Andrea Di Luca ◽  
Ville R. I. Kaila ◽  
Judy Hirst
Keyword(s):  
Electron Transfer ◽  
Complex I ◽  
Mammalian Cells ◽  
Membrane Surface ◽  
Proton Translocation ◽  
Structural Data ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Respiratory Complex ◽  
Respiratory Complex I ◽  
Ubiquinone 10

Respiratory complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in mammalian cells, powers ATP synthesis by using the energy from electron transfer from NADH to ubiquinone-10 to drive protons across the energy-transducing mitochondrial inner membrane. Ubiquinone-10 is extremely hydrophobic, but in complex I the binding site for its redox-active quinone headgroup is ∼20 Å above the membrane surface. Structural data suggest it accesses the site by a narrow channel, long enough to accommodate almost all of its ∼50-Å isoprenoid chain. However, how ubiquinone/ubiquinol exchange occurs on catalytically relevant timescales, and whether binding/dissociation events are involved in coupling electron transfer to proton translocation, are unknown. Here, we use proteoliposomes containing complex I, together with a quinol oxidase, to determine the kinetics of complex I catalysis with ubiquinones of varying isoprenoid chain length, from 1 to 10 units. We interpret our results using structural data, which show the hydrophobic channel is interrupted by a highly charged region at isoprenoids 4–7. We demonstrate that ubiquinol-10 dissociation is not rate determining and deduce that ubiquinone-10 has both the highest binding affinity and the fastest binding rate. We propose that the charged region and chain directionality assist product dissociation, and that isoprenoid stepping ensures short transit times. These properties of the channel do not benefit the exhange of short-chain quinones, for which product dissociation may become rate limiting. Thus, we discuss how the long channel does not hinder catalysis under physiological conditions and the possible roles of ubiquinone/ubiquinol binding/dissociation in energy conversion.

scholarly journals Symmetry-related proton transfer pathways in respiratory complex I

2017 ◽  
Vol 114 (31) ◽  
pp. E6314-E6321 ◽  
Author(s):  
Andrea Di Luca ◽  
Ana P. Gamiz-Hernandez ◽  
Ville R. I. Kaila
Keyword(s):  
Long Range ◽  
Complex I ◽  
Large Scale ◽  
Thermus Thermophilus ◽  
Site Directed Mutagenesis ◽  
Membrane Domain ◽  
Proton Coupled Electron Transfer ◽  
Quinone Reduction ◽  
Respiratory Chains ◽  
Respiratory Complex I

Complex I functions as the initial electron acceptor in aerobic respiratory chains of most organisms. This gigantic redox-driven enzyme employs the energy from quinone reduction to pump protons across its complete approximately 200-Å membrane domain, thermodynamically driving synthesis of ATP. Despite recently resolved structures from several species, the molecular mechanism by which complex I catalyzes this long-range proton-coupled electron transfer process, however, still remains unclear. We perform here large-scale classical and quantum molecular simulations to study the function of the proton pump in complex I from Thermus thermophilus. The simulations suggest that proton channels are established at symmetry-related locations in four subunits of the membrane domain. The channels open up by formation of quasi one-dimensional water chains that are sensitive to the protonation states of buried residues at structurally conserved broken helix elements. Our combined data provide mechanistic insight into long-range coupling effects and predictions for site-directed mutagenesis experiments.

scholarly journals A Quinol Anion as Catalytic Intermediate Coupling Proton Translocation With Electron Transfer in E. coli Respiratory Complex I

2021 ◽  
Vol 9 ◽  
Author(s):  
Franziska Nuber ◽  
Luca Mérono ◽  
Sabrina Oppermann ◽  
Johannes Schimpf ◽  
Daniel Wohlwend ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Complex I ◽  
Proton Translocation ◽  
Difference Spectrum ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Protonmotive Force ◽  
Respiratory Complex ◽  
Quinone Reduction ◽  
Vis Spectroscopy ◽  
Respiratory Complex I

Energy-converting NADH:ubiquinone oxidoreductase, respiratory complex I, plays a major role in cellular energy metabolism. It couples NADH oxidation and quinone reduction with the translocation of protons across the membrane, thus contributing to the protonmotive force. Complex I has an overall L-shaped structure with a peripheral arm catalyzing electron transfer and a membrane arm engaged in proton translocation. Although both reactions are arranged spatially separated, they are tightly coupled by a mechanism that is not fully understood. Using redox-difference UV-vis spectroscopy, an unknown redox component was identified in Escherichia coli complex I as reported earlier. A comparison of its spectrum with those obtained for different quinone species indicates features of a quinol anion. The re-oxidation kinetics of the quinol anion intermediate is significantly slower in the D213GH variant that was previously shown to operate with disturbed quinone chemistry. Addition of the quinone-site inhibitor piericidin A led to strongly decreased absorption peaks in the difference spectrum. A hypothesis for a mechanism of proton-coupled electron transfer with the quinol anion as catalytically important intermediate in complex I is discussed.

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