ATP Synthase

Junge, Wolfgang; Nelson, Nathan

doi:10.1146/annurev-biochem-060614-034124

Cited by 310 publications

(276 citation statements)

References 164 publications

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“…Our analysis shows that the rotary mechanism is faster than other possible mechanisms, particularly under challenging conditions, suggesting a possible evolutionary advantage. transported across the membrane (to the "out"-side) one at a time (8). In contrast, in the basic alternating-access mechanism (Figs.…”

Section: Significancementioning

confidence: 98%

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

Anandakrishnan

Zhang

Donovan-Maiye

et al. 2016

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

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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.ATP synthase | kinetic mechanism | free-energy landscape | nonequilibrium steady state | evolution T he F-ATPase performs molecular-level free-energy (FE) transduction to phosphorylate ADP and yield ATP, the primary energy carrier that drives a vast range of cellular processes. It spurred Mitchell's chemiosmotic hypothesis (1) and Boyer's now-validated proposal for the binding-change mechanism (2) in which a proton electrochemical gradient is transduced to rotationbased mechanical energy and then back to chemical FE as ADP is phosphorylated. The F-ATPase's two-domain uniaxial rotary structure is conserved across all three domains of life (3-6), and details of its function have been the subject of a multitude of studies (e.g., refs. 7-30).Here, we address a relatively narrow question with potentially significant evolutionary implications: Why is ATP synthesized by a rotary mechanism instead of a potentially much simpler alternating-access mechanism (Fig. 1)? Using thermodynamic and kinetic constraints, we address the question of whether evolution tends to arrive at optimal molecular processes (31), building on established concepts of optimality-derived evolutionary convergence (32, 33). Presumably, performance advantages in the central task of ATP synthesis would be under significant evolutionary pressure. Previous modeling studies of the F-ATPase have addressed structural and mechanistic questions about the rotary mechanism (e.g., refs. 11-20), but not the metaissue of the mechanism itself compared with alternatives.To assess whether the rotary mechanism possesses any intrinsic performance advantage, we constructed a series of kinetic models abstracted from known mechanisms (Fig. 1). Beyond the rotarybased model, we considered a series of alternating-access analogs (Fig. 2), building on the demonstrated capacity for ATP-hydrolyzing transporters to be driven in reverse to synthesize ATP (34, 35). The discrete-state models do not include structural details, bu...

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Section: Significancementioning

confidence: 98%

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

Anandakrishnan

Zhang

Donovan-Maiye

et al. 2016

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

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“…In chloroplasts, ATP synthase is located in the thylakoid membrane and comprises two major structural subcomplexes, CF 1 and CF 0 (von Ballmoos et al, 2009;Junge and Nelson, 2015). The CF 1 subcomplex is composed of five different subunits with a stoichiometry of a 3 b 3 g 1 d 1 « 1 , whereas the CF 0 subcomplex is comprised of four different subunits with a stoichiometry of I 1 II 1 III 14 IV 1 (Groth and Pohl, 2001;Vollmar et al, 2009).…”

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confidence: 99%

“…Together with the CF 1 « subunit, CF 1 g interacts with the c-ring (III 14 ) of the CF 0 subcomplex to form the "rotor." When ATP synthase is activated, efflux of protons drives the rotation of the rotor, and rotation of the g-subunit inside the a 3 b 3 hexagon induces conformational changes in the a 3 b 3 hexamer, resulting in the biosynthesis and release of ATP (Junge and Nelson, 2015).…”

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confidence: 99%

BIOGENESIS FACTOR REQUIRED FOR ATP SYNTHASE 3 Facilitates Assembly of the Chloroplast ATP Synthase Complex

et al. 2016

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Thylakoid membrane-localized chloroplast ATP synthases use the proton motive force generated by photosynthetic electron transport to produce ATP from ADP. Although it is well known that the chloroplast ATP synthase is composed of more than 20 proteins with a 3 b 3 g 1 « 1 d 1 I 1 II 1 III 14 IV 1 stoichiometry, its biogenesis process is currently unclear. To unravel the molecular mechanisms underlying the biogenesis of chloroplast ATP synthase, we performed extensive screening for isolating ATP synthase mutants in Arabidopsis (Arabidopsis thaliana). In the recently identified bfa3 (biogenesis factors required for ATP synthase 3) mutant, the levels of chloroplast ATP synthase subunits were reduced to approximately 25% of wild-type levels. In vivo labeling analysis showed that assembly of the CF 1 component of chloroplast ATP synthase was less efficient in bfa3 than in the wild type, indicating that BFA3 is required for CF 1 assembly. BFA3 encodes a chloroplast stromal protein that is conserved in higher plants, green algae, and a few species of other eukaryotic algae, and specifically interacts with the CF 1 b subunit. The BFA3 binding site was mapped to a region in the catalytic site of CF 1 b. Several residues highly conserved in eukaryotic CF 1 b are crucial for the BFA3-CF 1 b interaction, suggesting a coevolutionary relationship between BFA3 and CF 1 b. BFA3 appears to function as a molecular chaperone that transiently associates with unassembled CF 1 b at its catalytic site and facilitates subsequent association with CF 1 a during assembly of the CF 1 subcomplex of chloroplast ATP synthase.

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“…The stator consists of the α 3 β 3 catalytic head, the δb 2 peripheral stalk, and the a subunit. The γe-rotor shaft connects α 3 β 3 with the ac 10 proton translocator (3,5). The intact molecular motor has a mass of 525 kDa.…”

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confidence: 99%

Load-dependent destabilization of the γ-rotor shaft in F _O F ₁ ATP synthase revealed by hydrogen/deuterium-exchange mass spectrometry

Vahidi

Dunn

et al. 2016

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

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FoF1 is a membrane-bound molecular motor that uses proton-motive force (PMF) to drive the synthesis of ATP from ADP and Pi. Reverse operation generates PMF via ATP hydrolysis. Catalysis in either direction involves rotation of the γε shaft that connects the α3β3 head and the membrane-anchored cn ring. X-ray crystallography and other techniques have provided insights into the structure and function of FoF1 subcomplexes. However, interrogating the conformational dynamics of intact membrane-bound FoF1 during rotational catalysis has proven to be difficult. Here, we use hydrogen/deuterium exchange mass spectrometry to probe the inner workings of FoF1 in its natural membrane-bound state. A pronounced destabilization of the γ C-terminal helix during hydrolysis-driven rotation was observed. This behavior is attributed to torsional stress in γ, arising from γ⋅⋅⋅α3β3 interactions that cause resistance during γ rotation within the apical bearing. Intriguingly, we find that destabilization of γ occurs only when FoF1 operates against a PMF-induced torque; the effect disappears when PMF is eliminated by an uncoupler. This behavior resembles the properties of automotive engines, where bearings inflict greater forces on the crankshaft when operated under load than during idling.

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ATP Synthase

Cited by 310 publications

References 164 publications

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

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

BIOGENESIS FACTOR REQUIRED FOR ATP SYNTHASE 3 Facilitates Assembly of the Chloroplast ATP Synthase Complex

Load-dependent destabilization of the γ-rotor shaft in F _O F ₁ ATP synthase revealed by hydrogen/deuterium-exchange mass spectrometry

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ATP Synthase

Cited by 310 publications

References 164 publications

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

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

BIOGENESIS FACTOR REQUIRED FOR ATP SYNTHASE 3 Facilitates Assembly of the Chloroplast ATP Synthase Complex

Load-dependent destabilization of the γ-rotor shaft in F O F 1 ATP synthase revealed by hydrogen/deuterium-exchange mass spectrometry

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Load-dependent destabilization of the γ-rotor shaft in F _O F ₁ ATP synthase revealed by hydrogen/deuterium-exchange mass spectrometry