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F₁-ATPase Rotary Mechanism: Interpreting Results of Diverse Experimental Modes With an Elastic Coupling Theory

Volkán-Kacsó, Sándor and Marcus, Rudolph A. (2022) F₁-ATPase Rotary Mechanism: Interpreting Results of Diverse Experimental Modes With an Elastic Coupling Theory. Frontiers in Microbiology, 13 . Art. No. 861855. ISSN 1664-302X. PMCID PMC9072658. doi:10.3389/fmicb.2022.861855.

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In this chapter, we review single-molecule observations of rotary motors, focusing on the general theme that their mechanical motion proceeds in substeps with each substep described by an angle-dependent rate constant. In the molecular machine F₁-ATPase, the stepping rotation is described for individual steps by forward and back reaction rate constants, some of which depend strongly on the rotation angle. The rotation of a central shaft is typically monitored by an optical probe. We review our recent work on the theory for the angle-dependent rate constants built to treat a variety of single-molecule and ensemble experiments on the F₁-ATPase, and relating the free energy of activation of a step to the standard free energy of reaction for that step. This theory, an elastic molecular transfer theory, provides a framework for a multistate model and includes the probe used in single-molecule imaging and magnetic manipulation experiments. Several examples of its application are the following: (a) treatment of the angle-dependent rate constants in stalling experiments, (b) use of the model to enhance the time resolution of the single-molecule imaging apparatus and to detect short-lived states with a microsecond lifetime, states hidden by the fluctuations of the imaging probe, (c) treatment of out-of-equilibrium “controlled rotation” experiments, (d) use of the model to predict, without adjustable parameters, the angle-dependent rate constants of nucleotide binding and release, using data from other experiments, and (e) insights obtained from correlation of kinetic and cryo-EM structural data. It is also noted that in the case where the release of ADP would be a bottleneck process, the binding of ATP to another site acts to accelerate the release by 5–6 orders of magnitude. The relation of the present set of studies to previous and current theoretical work in the field is described. An overall goal is to gain mechanistic insight into the biological function in relation to structure.

Item Type:Article
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URLURL TypeDescription CentralArticle
Volkán-Kacsó, Sándor0000-0003-3327-2865
Marcus, Rudolph A.0000-0001-6547-1469
Additional Information:© 2022 Volkán-Kacsó and Marcus. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 25 January 2022; Accepted: 28 March 2022; Published: 22 April 2022. We would like to acknowledge the helpful discussions of the Cryo-EM and related data with Ricardo Matute and the helpful analysis of Nayree Panossian, Oganes Khatchikian, and Nathan Suiter of the temperature-dependent and single-molecule kinetic data of Watanabe and Noji (2014). Author Contributions. SV-K and RM planned and performed the research and wrote the manuscript. All authors contributed to the article and approved the submitted version. This work was supported by the Office of the Naval Research and the James W. Glanville Foundation. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Edited by: Tom Duncan, Upstate Medical University, United States Reviewed by: Abhishek Singharoy, Arizona State University, United States Kwangho Nam, University of Texas at Arlington, United States
Funding AgencyGrant Number
Office of Naval Research (ONR)UNSPECIFIED
James W. Glanville FoundationUNSPECIFIED
Subject Keywords:F1-ATPase, stepping rotation of F1-ATPase, rotary biomolecular motors, cryo-electron microscopy, single-molecule imaging, multi-state theory, ATP binding, concerted kinetics
PubMed Central ID:PMC9072658
Record Number:CaltechAUTHORS:20220520-231783000
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Official Citation:Volkán-Kacsó S and Marcus RA (2022) F1-ATPase Rotary Mechanism: Interpreting Results of Diverse Experimental Modes With an Elastic Coupling Theory. Front. Microbiol. 13:861855. doi: 10.3389/fmicb.2022.861855
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:114862
Deposited By: George Porter
Deposited On:24 May 2022 14:14
Last Modified:24 May 2022 14:14

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