Coulombic Organization in Membrane-Embedded Rotary Motor of ATP Synthase.

Abstract

The electrochemical potential difference of protons across the membrane is used to synthesize ATP through the proton-motive rotatory motion of the membrane-embedded region of ATP synthase called Fo. In this study, we illuminate the unsolved proton-motive rotary mechanism of Fo on the basis of atomistic simulation with full description of protein, lipid, and water molecules, and highlight the underlying Coulombic design. We first show that a water channel is spontaneously formed at the interfacial region between the rotor (c-ring) and the stator (a-subunit). The observed water channel is a full channel penetrating the membrane, but a Coulomb barrier by a strictly conserved arginine of the a-subunit dominates at the midpoint of the full channel, preventing proton leakage. Our molecular dynamics simulation further demonstrates that the Coulomb attraction between the arginine and the essential glutamic acid of the c-subunit drives the c-ring rotation. We finally illustrate that the charge-state changes of the glutamic acids, enabled by the electrochemical potential difference of proton and the thermal motion, can produce unidirectional rotation of the c-ring.