Biophysical comparison of ATP synthesis mechanisms shows a kinetic advantage for the rotary process

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 syste...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 113; no. 40; pp. 11220 - 11225
Main Authors Anandakrishnan, Ramu, Zhang, Zining, Donovan-Maiye, Rory, Zuckerman, Daniel M.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 04.10.2016
Subjects
Adenosine triphosphatase
Adenosine Triphosphate - biosynthesis
ATP
Biological Sciences
Biophysical Phenomena
Comparative analysis
Electrochemistry
Kinetics
Models, Biological
Proton-Motive Force
Rotation
Solutions
Thermodynamics
ATP synthase
evolution
free-energy landscape
kinetic mechanism
nonequilibrium steady state
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Summary: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.
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1R.A. and Z.Z. contributed equally to this work.
Author contributions: R.A., Z.Z., and D.M.Z. designed research; R.A., Z.Z., and D.M.Z. performed research; R.A., Z.Z., and R.D.-M. contributed new reagents/analytic tools; R.A., Z.Z., R.D.-M., and D.M.Z. analyzed data; and R.A. and D.M.Z. wrote the paper.
3Present address: OHSU Center for Spatial Systems Biomedicine and Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239.
Edited by Ken A. Dill, Stony Brook University, Stony Brook, NY, and approved July 29, 2016 (received for review May 26, 2016)
2Present address: Biomedical Division, Edward Via College of Osteopathic Medicine, Blacksburg, VA 24060.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1608533113