TY - JOUR
T1 - Biophysical comparison of ATP synthesis mechanisms shows a kinetic advantage for the rotary process
AU - Anandakrishnan, Ramu
AU - Zhang, Zining
AU - Donovan-Maiye, Rory
AU - Zuckerman, Daniel M.
N1 - Publisher Copyright:
© 2016, National Academy of Sciences. All rights reserved.
PY - 2016/10/4
Y1 - 2016/10/4
N2 - 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.
AB - 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.
KW - ATP synthase
KW - Evolution
KW - Free-energy landscape
KW - Kinetic mechanism
KW - Nonequilibrium steady state
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U2 - 10.1073/pnas.1608533113
DO - 10.1073/pnas.1608533113
M3 - Article
C2 - 27647911
AN - SCOPUS:84989930967
SN - 0027-8424
VL - 113
SP - 11220
EP - 11225
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 40
ER -