Intrinsic electrostatics of ATP synthase modulate the proton motive force across species

Abstract

ATP synthase functions within a highly structured electrostatic environment, but comparative information on its intrinsic protein electrostatics across species remains limited. Here, we analyze 178 crystallographic and cryo-EM ATP synthase structures from 17 species using a consistent Poisson-Boltzmann workflow. The calculations reveal reproducible species-dependent axial electrostatic asymmetries across the Fo-F1 complex, with plane-averaged potential differences of approximately 10-20 mV between an entry-side axial window (z = -10 to +10 Angstrom) and an exit-side axial window (z = +50 to +70 Angstrom) in several taxa. The five available Homo sapiens structures display a consistent axial electrostatic orientation within this species, whereas broader variation is observed across the full multi-species dataset; these two observations reflect within-species and across-species comparisons, respectively. Membrane-mimicking low-dielectric slabs amplify the profiles and demonstrate the sensitivity of the electrostatic landscape to dielectric boundary conditions. We interpret these quantities as static, structure-derived electrostatic descriptors, not as independent membrane voltages or additive proton-motive-force terms. The results provide a comparative electrostatic atlas of ATP synthase and suggest testable hypotheses concerning local proton-pathway energetics, structural evolution, and inhibitor sensitivity.