Elastic coupling power stroke mechanism of the F
            <sub>1</sub>
            -ATPase molecular motor

Martin, James L.; Ishmukhametov, Robert; Spetzler, David; Hornung, Tassilo; Frasch, Wayne D.

doi:10.1073/pnas.1803147115

Cited by 50 publications

(79 citation statements)

References 71 publications

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“…For the intermediate, we postulated a state containing both the incoming ATP and outgoing ADP, similar to the state postulated by Walker et al (25) in which all 3 β subunits are occupied by nucleotides. Alternatively, sequential kinetics for the ATP binding/ADP release was suggested (3,26,27), but a kinetic intermediate was previously undetected. Its ∼10-µs lifetime suggests a microsecond timescale for the lifetime of the proposed intermediate state.…”

Section: Discussionmentioning

confidence: 99%

Method to extract multiple states in F ₁ -ATPase rotation experiments from jump distributions

Volkan-Kacso

Zhu

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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A method is proposed for analyzing fast (10 µs) single-molecule rotation trajectories in F 1 adenosinetriphosphatase (F 1 -ATPase). This method is based on the distribution of jumps in the rotation angle that occur in the transitions during the steps between subsequent catalytic dwells. The method is complementary to the "stalling" technique devised by H. Noji et al. [Biophys. Rev. 9, 103-118, 2017], and can reveal multiple states not directly detectable as steps. A bimodal distribution of jumps is observed at certain angles, due to the system being in either of 2 states at the same rotation angle. In this method, a multistate theory is used that takes into account a viscoelastic fluctuation of the imaging probe. Using an established sequence of 3 specific states, a theoretical profile of angular jumps is predicted, without adjustable parameters, that agrees with experiment for most of the angular range. Agreement can be achieved at all angles by assuming a fourth state with an ∼10 µs lifetime and a dwell angle about 40 • after the adenosine 5 -triphosphate (ATP) binding dwell. The latter result suggests that the ATP binding in one β subunit and the adenosine 5 -diphosphate (ADP) release from another β subunit occur via a transient whose lifetime is ∼10 µs and is about 6 orders of magnitude smaller than the lifetime for ADP release from a singly occupied F 1 -ATPase. An internal consistency test is given by comparing 2 independent ways of obtaining the relaxation time of the probe. They agree and are ∼15 µs.F-ATPase | single-molecule imaging | concerted dynamics | 4-state model | ADP release Author contributions: S† References and equations used to estimate the quantities in columns 3-8 are grouped in 6 groups in order according to the columns to which they refer.Groups are separated by semicolons, e.g., items before the first semicolon refer to column 3.Volkán-Kacsó et al.

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Section: Discussionmentioning

confidence: 99%

Method to extract multiple states in F ₁ -ATPase rotation experiments from jump distributions

Volkan-Kacso

Zhu

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Some authors suggest energy is stored by coiling of the g-subunit two-helix bundle (10); others propose that energy is stored at the 'foot', where g and e are attached to the c-ring (9). Recent cryo-EM studies resolving rotary states of mitochondrial (11), bacterial (12) and chloroplast (13) ATP synthase have all found that the central stalk rotates as a rigid body.…”

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confidence: 99%

Rotary substates of mitochondrial ATP synthase reveal the basis of flexible F₁-F_o coupling

Murphy

Klusch

Langer

et al. 2019

Preprint

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F 1 F o -ATP synthases play a central role in cellular metabolism, making the energy of the protonmotive force across a membrane available for a large number of energy-consuming processes. We determined the single-particle cryo-EM structure of active dimeric ATP synthase from mitochondria of Polytomella sp. at 2.7-2.8 Å resolution. Separation of 13 well-defined rotary substates by 3D classification provides a detailed picture of the molecular motions that accompany c-ring rotation and result in ATP synthesis. Crucially, the F 1 head rotates along with the central stalk and c-ring rotor for the first ~30° of each 120° primary rotary step. The joint movement facilitates flexible coupling of the stoichiometrically mismatched F 1 and F o subcomplexes. Flexibility is mediated primarily by the interdomain hinge of the conserved OSCP subunit, a well-established target of physiologically important inhibitors. Our maps provide atomic detail of the c-ring/a-subunit interface in the membrane, where protonation and deprotonation of c-ring cGlu111 drives rotary catalysis. An essential histidine residue in the lumenal proton access channel binds a strong non-peptide density assigned to a metal ion that may facilitate c-ring protonation, as its coordination geometry changes with c-ring rotation. We resolve ordered water molecules in the proton access and release channels and at the gating aArg239 that is critical in all rotary ATPases. We identify the previously unknown ASA10 subunit and present complete de novo atomic models of subunits ASA1-10, which make up the two interlinked peripheral stalks that stabilize the Polytomella ATP synthase dimer. One Sentence Summary:Mechanisms of proton translocation and flexible F 1 -F o coupling by rotary substates in a mitochondrial ATP synthase dimer Main Text:Mitochondria carry out controlled oxidation of reduced substrates to generate an electrochemical gradient across the inner mitochondrial membrane. Movement of protons down the gradient through the F 1 F o -ATP synthase drives the production of the soluble energy carrier ATP by rotary catalysis. The ATP synthases consist of two connected nanomotors: the membrane-embedded F o subcomplex where proton translocation generates torque, and the soluble F 1 subcomplex where the

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“…The resulting change in contacts is likely to play an important role, as suggested in our previous publication (23). Recent simultaneous single-molecule fluorescence resonance energy transfer (FRET) and rotation measurements (26) support this picture of the rotation cycle, as does the paper by Martin et al (19). In human F 1 -ATPase, on the other hand, it has recently been shown that the rotation takes place in 3 substeps: 0°→ 65°during ATP binding/ADP release, 65°→ 90°with P i release, and 90°→ 120°with ATP hydrolysis (28).…”

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confidence: 52%

“…This result was subsequently refined to show that the rotation occurs in 40°and 80°substeps (11)(12)(13). [In this work, we use the 40°and 80°notation following Adachi et al (12), although the choice is somewhat arbitrary and other papers use other values (11,(14)(15)(16)(17)(18)(19).] Through these studies, as well as others (20,21), in conjunction with simulations (16,(22)(23)(24), a detailed molecular description of each of the 2 substeps in the γ-subunit rotation cycle was established ( Fig.…”

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confidence: 99%

Insights into the origin of the high energy-conversion efficiency of F ₁ -ATPase

Nam

Karplus

2019

Proc. Natl. Acad. Sci. U.S.A.

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Our understanding of the rotary-coupling mechanism of F1-ATPase has been greatly enhanced in the last decade by advances in X-ray crystallography, single-molecular imaging, and theoretical models. Recently, Volkán-Kacsó and Marcus [S. Volkán-Kacsó, R. A. Marcus, Proc. Natl. Acad. Sci. U.S.A. 112, 14230 (2015)] presented an insightful thermodynamic model based on the Marcus reaction theory coupled with an elastic structural deformation term to explain the observed γ-rotation angle dependence of the adenosine triphosphate (ATP)/adenosine diphosphate (ADP) exchange rates of F1-ATPase. Although the model is successful in correlating single-molecule data, it is not in agreement with the available theoretical results. We describe a revision of the model, which leads to consistency with the simulation results and other experimental data on the F1-ATPase rotor compliance. Although the free energy liberated on ATP hydrolysis by F1-ATPase is rapidly dissipated as heat and so cannot contribute directly to the rotation, we show how, nevertheless, F1-ATPase functions near the maximum possible efficiency. This surprising result is a consequence of the differential binding of ATP and its hydrolysis products ADP and Pi along a well-defined pathway.

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Elastic coupling power stroke mechanism of the F ₁ -ATPase molecular motor

Cited by 50 publications

References 71 publications

Method to extract multiple states in F ₁ -ATPase rotation experiments from jump distributions

Method to extract multiple states in F ₁ -ATPase rotation experiments from jump distributions

Rotary substates of mitochondrial ATP synthase reveal the basis of flexible F₁-F_o coupling

Insights into the origin of the high energy-conversion efficiency of F ₁ -ATPase

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Elastic coupling power stroke mechanism of the F 1 -ATPase molecular motor

Cited by 50 publications

References 71 publications

Method to extract multiple states in F 1 -ATPase rotation experiments from jump distributions

Method to extract multiple states in F 1 -ATPase rotation experiments from jump distributions

Rotary substates of mitochondrial ATP synthase reveal the basis of flexible F1-Fo coupling

Insights into the origin of the high energy-conversion efficiency of F 1 -ATPase

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Elastic coupling power stroke mechanism of the F ₁ -ATPase molecular motor

Method to extract multiple states in F ₁ -ATPase rotation experiments from jump distributions

Method to extract multiple states in F ₁ -ATPase rotation experiments from jump distributions

Rotary substates of mitochondrial ATP synthase reveal the basis of flexible F₁-F_o coupling

Insights into the origin of the high energy-conversion efficiency of F ₁ -ATPase