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

Ramu Anandakrishnan, Zining Zhang, Rory Donovan-Maiye, Daniel M. Zuckerman

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)11220-11225
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number40
DOIs
StatePublished - Oct 4 2016

Keywords

  • ATP synthase
  • Evolution
  • Free-energy landscape
  • Kinetic mechanism
  • Nonequilibrium steady state

ASJC Scopus subject areas

  • General

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