title: Biophysical comparison of ATP synthesis mechanisms shows a kinetic advantage for the rotary process.
abstract: The ATP synthase (F-ATPase) is a highly complex rotary machine that synthesizes ATP, powered by a proton electrochemical gradient. Why did evolution select such an elaborate mechanism over arguably simpler alternating-access processes that can be reversed to perform ATP synthesis? We studied a systematic enumeration of alternative mechanisms, using numerical and theoretical means. When the alternative models are optimized subject to fundamental thermodynamic constraints, they fail to match the kinetic ability of the rotary mechanism over a wide range of conditions, particularly under low-energy conditions. We used a physically interpretable, closed-form solution for the steady-state rate for an arbitrary chemical cycle, which clarifies kinetic effects of complex free-energy landscapes. Our analysis also yields insights into the debated "kinetic equivalence" of ATP synthesis driven by transmembrane pH and potential difference. Overall, our study suggests that the complexity of the F-ATPase may have resulted from positive selection for its kinetic advantage.
authors.affiliation: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260.
authors.forename: Ramu
authors.initials: R
authors.lastname: Anandakrishnan
authors.affiliation: Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zining
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260.
authors.forename: Rory
authors.initials: R
authors.lastname: Donovan-Maiye
authors.affiliation: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260; ddmmzz@pitt.edu.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Zuckerman
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D055592:Biophysical Phenomena; D007700:Kinetics; D008954:Models, Biological; D018892:Proton-Motive Force; D012399:Rotation; D012996:Solutions; D013816:Thermodynamics
chemical_list: D012996:Solutions; D000255:Adenosine Triphosphate
keywords: ATP synthase; evolution; free-energy landscape; kinetic mechanism; nonequilibrium steady state