Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 40, Pages 11220-11225Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1608533113
Keywords
ATP synthase; kinetic mechanism; free-energy landscape; nonequilibrium steady state; evolution
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Funding
- China Scholarship Council
- University of Pittsburgh, NIH [P41-GM103712]
- National Science Foundation [MCB-1119091]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1701846] Funding Source: National Science Foundation
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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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