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

Abstract

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.

Redox-coupled proton pumping drives carbon concentration in the photosynthetic complex I

“…The structural architecture thus supports that the long-range protonation signal could be triggered by dissociation of conserved ion-pairs in the antiporter-like subunits that leads to lateral proton transfer in the proton channels by coupled conformational and hydration changes ( Fig. 4) 16,19,20 .…”

“…The modular membrane domain extends up to 200 Å away from the PQ reduction site, and it comprises the antiporter-like subunits NdhA, NdhB, NdhD3, and NdhF3, as well as the smaller transmembrane (TM) subunits NdhC/E/G/L. These subunits contain a chain of buried charged residues that establish central elements of the proton-pumping machinery [11][12][13][14][15][16][17]19,20 , with the isoform-specific NdhD3 and NdhF3 subunits at the terminal end of the enzyme (Fig. 1d, see below).…”

“…7). The proton channels are established across the membrane around charged residues in the broken helices TM7 and TM12 of the antiporter-like subunits NdhB, NdhD3 19,20 , and also in NdhA/C/E/G ( Figs. 1d and 3, and Supplementary Fig.…”

Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90

“…Our data indicate that the conformational switching takes place via a conserved network of ion pairs between the N-and M-domains of the enzyme involving, e.g., E381 ( Supplementary Figs. 7 and 19), with mechanistic similarities to, e.g., respiratory complex I, a mitochondrial redox-driven proton pump where quinone reduction triggers proton pumping, up to 200 Å from the active site, by conformational changes in a network of conserved ion pairs [34][35][36][37] . It is puzzling that although the R32A variant is not viable in vivo and unable to properly form a closed compact state, the enzyme still hydrolyses ATP with an unchanged ADP-release rate.…”

Beyond esterase‐like activity of serum albumin. Histidine‐(nitro)phenol radical formation in conversion cascade of p‐nitrophenyl acetate and the role of infrared light

“…The electron transfer in general is crucial for energy conversion in cells. 24,25 In this context, it has been recognized that water molecules can form structural and functional bridges between OH groups and N atoms in proteins. 26 Such bridges (water wires) can conduct protons and effectively support proton-coupled electron transfer mechanism.…”