Nucleotide Exchange Mechanism Involving Angle-Dependent Rate Constants Extracted from F1-ATPase Single-Molecule Rotation Trajectories

Evidence has been mounting that in the rotational cycle of F1-ATPase there is a concerted ATP binding and ADP release that yields a million-fold acceleration in the rate of the product ADP release. We developed a theory of reaction kinetics to investigate the relationship between the concerted nucleotide exchange and previous single-molecule forced rotation data from AdachiK., Nat. Commun. 2012, 3, 1022 22929779 . We extracted from these data angle-dependent rate constants for nucleotide binding and release. The rate constants were then used in a unified kinetic scheme, also consistent with other single-molecule and ensemble experiments, to obtain analytical equations for nucleotide occupancy change events from nano- to millimolar ATP concentrations. A theory-experiment comparison revealed novel evidence about the concerted mechanism: it is determined by correlated conformational changes in the F1-ATPase ring, and its kinetic signature is a unified angle-dependent function of the nucleotide binding and release rate constants, which is independent of ATP concentration.

• Publication year

  2025

• Venue

  Journal of Physical Chemistry B

• Publication date

  2025-11-10

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1021/acs.jpcb.5c04403PMID 41212623PMCID 12814531
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Catalytic dwell oscillations complete the F1-ATPase mechanism

  2025cited by this paper
• The molecular structure of an axle-less F1-ATPase.

  2024cited by this paper
• Allosteric crosstalk in modular proteins: Function fine-tuning and drug design

  2023cited by this paper
• Molecular mechanism and energetics of coupling between substrate binding and product release in the F1-ATPase catalytic cycle

  2023cited by this paper
• Mitochondrial ATP Synthase is a Target of Oxidative Stress in Neurodegenerative Diseases

  2022cited by this paper
• The development of single molecule force spectroscopy: from polymer biophysics to molecular machines

  2022cited by this paper
• Defueling the cancer: ATP synthase as an emerging target in cancer therapy

  2021cited by this paper
• High ATP Production Fuels Cancer Drug Resistance and Metastasis: Implications for Mitochondrial ATP Depletion Therapy

  2021cited by this paper
• Rotary catalysis of bovine mitochondrial F1-ATPase studied by single-molecule experiments

  2020cited by this paper
• Essential

  2020cited by this paper
• The 3 × 120° rotary mechanism of Paracoccus denitrificans F1-ATPase is different from that of the bacterial and mitochondrial F1-ATPases

  2020cited by this paper
• The ribosome modulates folding inside the ribosomal exit tunnel

  2020cited by this paper
• Method to extract multiple states in F1-ATPase rotation experiments from jump distributions

  2019cited by this paper
• Molecular switch-like regulation in motor proteins

  2018cited by this paper
• Theory of long binding events in single-molecule–controlled rotation experiments on F1-ATPase

  2017cited by this paper
• What can be learned about the enzyme ATPase from single-molecule studies of its subunit F1?

  2017cited by this paper
• Theory for rates, equilibrium constants, and Brønsted slopes in F1-ATPase single molecule imaging experiments

  2015cited by this paper
• The Resolution Revolution

  2014cited by this paper
• Timing of inorganic phosphate release modulates the catalytic activity of ATP-driven rotary motor protein

  2014cited by this paper
• The Structural Basis of ATP as an Allosteric Modulator

  2014cited by this paper
• Allosteric communication in the dynein motor domain.

  2014cited by this paper
• Chemomechanical coupling of human mitochondrial F1-ATPase motor.

  2014cited by this paper
• Controlled rotation of the F1-ATPase reveals differential and continuous binding changes for ATP synthesis

  2012cited by this paper
• Mechanical modulation of catalytic power on F1-ATPase.

  2011influential reference
• High-Speed Atomic Force Microscopy Reveals Rotary Catalysis of Rotorless F1-ATPase

  2011cited by this paper
• Chemo-mechanical coupling in F(1)-ATPase revealed by catalytic site occupancy during catalysis.

  2010cited by this paper
• Axle-Less F1-ATPase Rotates in the Correct Direction

  2008cited by this paper
• Allosteric Communication in Myosin V: From Small Conformational Changes to Large Directed Movements

  2008cited by this paper
• Coupling of rotation and catalysis in F(1)-ATPase revealed by single-molecule imaging and manipulation.

  2007influential reference
• Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase

  2001influential reference
• Free energy reconstruction from nonequilibrium single-molecule pulling experiments

  2001cited by this paper
• Path-ensemble averages in systems driven far from equilibrium

  1999cited by this paper
• Energy transduction in the F1 motor of ATP synthase

  1998cited by this paper
• Nonequilibrium Equality for Free Energy Differences

  1996cited by this paper
• Structure at 2.8 Â resolution of F1-ATPase from bovine heart mitochondria

  1994cited by this paper
• Application of Marcus theory to gas-phase SN2 reactions: experimental support of the Marcus theory additivity postulate

  1993cited by this paper
• Complete kinetic and thermodynamic characterization of the unisite catalytic pathway of Escherichia coli F1-ATPase. Comparison with mitochondrial F1-ATPase and application to the study of mutant enzymes.

  1988cited by this paper

• No citing papers are available for this paper.