Rotational Mechanism of FO Motor in the F-Type ATP Synthase Driven by the Proton Motive Force

Abstract

In FOF1 ATP synthase, driven by the proton motive force across the membrane, the FO motor rotates the central rotor and induces conformational changes in the F1 motor, resulting in ATP synthesis. Recently, many near-atomic resolution structural models have been obtained using cryo-electron microscopy. Despite high resolution, however, static information alone cannot elucidate how and where the protons pass through the FO and how proton passage is coupled to FO rotation. Here, we review theoretical and computational studies based on FO structure models. All-atom molecular dynamics (MD) simulations elucidated changes in the protonation/deprotonation of glutamate—the protein-carrier residue—during rotation and revealed the protonation states that form the “water wire” required for long-range proton hopping. Coarse-grained MD simulations unveiled a free energy surface based on the protonation state and rotational angle of the rotor. Hybrid Monte Carlo and MD simulations showed how proton transfer is coupled to rotation.

Why are spontaneous bio photons observed only in living organisms? The key role of the proton current in ultra-weak photon emission

“…At this point, the essential role of water in the functioning of the F 0 motor unit should be emphasized. Water is necessary for formation the proton conduction channels 23,27,28 , protonic p-n junctions [4][5][6][7] and the light emission (Fig. 5) 2,3 .…”

“…Marked grey F 0 F 1 complex (a) and F 0 unit (b) in ATP synthase/ATPase (a modified drawing based on publication 18 ). (c) The proton flow in the F 0 -ATP synthase (including C-ring) protonic p-n junction system 37 (a scheme based on the structure of ATP synthase/ATPase from 18, 24, 27, 28, 29 ). Preferred (“forward”) proton flow direction with possible light emission is from the “p” to “n” area, like in a protonic diode H + LED 2, 4, 5 .…”

“…2) allows the use of protonic H + LED as a new broadband light source, ideally suited to mitochondria-oriented low-intensity light therapy 37 .Our results explain why spontaneous biophotons (UPE) are observed only in living organisms, tissues and cells 21 . This is due to the constant flow of protons in the active ATP synthase/ATPase 23 and in the mitochondria in general 25-28 , which is necessary both for life and for the emission of light (observed as bio photons).…”

Current Trends and Changes in Use of Membrane Molecular Dynamics Simulations within Academia and the Pharmaceutical Industry

“…This is not simply related to number of elements contained in the models, but the size of simulation dimensions. We have already observed this, first with simulations of the light harvesting system, Mitochondrial ATP Synthase and Ribosomes without endoplasmic reticulum membranes, each simulation containing dozens of proteins, nucleic acids and membrane components or other macromolecular components [ 69 , 176 , 177 ]. Currently, the human brain project now maintains an MD database for simulations involving membrane proteins, membranes and related projects.…”

Mechanism of ATP hydrolysis dependent rotation of ATP synthases

“…F-type ATP synthases, FoF1, exist in the inner membrane of mitochondria, the plasma membrane of bacteria, and the thylakoid membrane of chloroplasts, while Archaea and some bacteria express the homologous Vtype ATP synthases, called V/A-ATPases [4][5][6][7][8] . FoF1 consists of a hydrophilic F1 domain containing three catalytic sites 9 , and a hydrophobic Fo domain housing a proton translocation channel 10,11 (Fig. 1a).…”