Dependence of thermodynamic efficiency of proton pumps on frequency of oscillatory concentration of ATP.

Schell, Mark; Kundu, K.; Ross, John

doi:10.1073/pnas.84.2.424

Cited by 29 publications

(10 citation statements)

References 20 publications

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“…The efficiency of nuclear export is expected to be reduced if the RanGTP concentration decreases gradually on the cytoplasmic side of the NPC, even at a fixed ratio of nuclear and cytoplasmic RanGTP concentration. In addition, temporal changes in the rate of energy supply in the form of ATP or GTP might influence the efficiency of coupling (14)(15)(16).…”

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The strategy for coupling the RanGTP gradient to nuclear protein export

Becskei

Mattaj

2003

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

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The Ran GTPase plays critical roles in both providing energy for and determining the directionality of nucleocytoplasmic transport. The mechanism that couples the RanGTP gradient to nuclear protein export will determine the rate of and limits to accumulation of export cargoes in the cytoplasm, but is presently unknown. We reasoned that plausible coupling mechanisms could be distinguished by comparing the rates of reverse motion of export cargoes through the nuclear pore complex (NPC) with the predictions of a mathematical model. Measurement of reverse export rates in Xenopus oocytes revealed that nuclear export signals can facilitate RanGTP-dependent cargo movement into the nucleus against the RanGTP gradient at rates comparable to export rates. Although export cargoes with high affinity for their receptor are exported faster than those with low affinity, their reverse transport is also greater. The ratio of the rates of reverse and forward export of a cargo is proportional to its rate of diffusion through the NPC, i.e., to the ability of the cargo to penetrate the NPC permeability barrier. The data substantiate a diffusional mechanism of coupling and suggest the existence of a high concentration of RanGTP-receptor complexes within the NPC that decreases sharply at the cytoplasmic boundary of the NPC permeability barrier. T ransport of macromolecules between the nucleus and cytoplasm (1, 2) is generally an active, receptor-mediated process. A large majority of characterized transport events involve members of the importin ␤ family of import and export receptors. The Ran GTPase, in its GTP state, binds to these receptors and regulates their interaction with cargos in a compartmentspecific manner. Transport across the nuclear envelope (NE) occurs through nuclear pore complexes (NPCs), large proteinaceous structures that penetrate the NE and form aqueous channels. NPCs act as permeability barriers through which specific cargos are translocated by transport receptor-mediated facilitated diffusion.Proteins containing a leucine-rich nuclear export signal (NES) form an export complex in the nucleus by binding cooperatively with RanGTP to the export receptor CRM1 (1-5). On translocation through the NPC, export complexes are generally dissociated by the action of RanBP1 or RanBP2 and RanGAP in the cytoplasm, which together induce Ran to hydrolyze bound GTP and thus render export complex dissociation irreversible (1, 2, 6-8). For the completion of a nuclear export cycle, RanGDP is reimported into the nucleus (9, 10) and the bound GDP is exchanged to GTP by Ran's guanosine nucleotide exchange factor, RCC1. The reactions mediated by nuclear RCC1 and cytoplasmic RanGAP generate a gradient of RanGTP concentration across the NPC (11), which in turn, because of its influence on export receptor-cargo interactions, drives the vectorial movement of export cargoes. A similar logic applies to all known Ran-dependent nucleocytoplasmic transport events (1, 2). Despite the identification of the components of the export machinery and th...

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“…To understand the mechanism of coupling, however, it is crucial to examine the process under in vivo conditions in which both the synergy of all (e.g., refs. 26 and 27) factors relevant for the export process and the natural flux rates of the reactions of the RanGTP cycle are preserved (14)(15)(16).…”

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The strategy for coupling the RanGTP gradient to nuclear protein export

Becskei

Mattaj

2003

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

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“…Damped oscillatory behavior has been observed in an adenosine triphosphate (ATP)-driven proton pump (5). Ester hydrolysis by immobilized papain causes pH oscillations at the electrode upon which the papain is coated (6).Predictions have been made that the power output, the dissipation (for isothermal reactions, the product of AG and the rate) and hence the efficiency of nonlinear biochemical systems may be changed depending upon the mode of supply of reactants (steady or oscillatory) (7,8), with the same average consumption of reactants in either the oscillatory or steady mode ofsupply. We show experimentally that the mode of supply of reactants, steady or oscillatory, to a nonlinear, non-equilibrium biochemical reaction can determine the steady-state concentrations of the reaction.…”

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Changes in Mean Concentration, Phase Shifts, and Dissipation in a Forced Oscillatory Reaction

Lazar

Ross

1990

Science

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Experiments are presented that confirm earlier predictions that the mode of supply of reactants to a nonlinear (bio)chemical reaction determines or controls concentrations at steady states far from equilibrium. The oxidation of nicotinamide adenine dinucleotide (NADH) catalyzed by the enzyme horseradish peroxidase with continuous input of oxygen was studied; NAD+ is continuously recycled to NADH through a glucose-6-phosphate dehydrogenase system. A comparison of steady-state concentrations is made with an oscillatory oxygen input and a constant input at the same average oxygen input for both modes. By varying the frequency and amplitude of the perturbation (O2 influx), the following may be changed: the average concentration of NADH; the Gibbs free energy difference delta G of the reactants and products at steady state; the average rate of the reaction; the phase relation between the oscillatory rate and delta G; and the dissipation. These results confirm the possibility of an "alternating current chemistry," of control and optimization of thermodynamic efficiency and dissipation by means of external variation of constraints in classes of nonlinear reactions and biological pumps, and of improvements of the yield in such reactions (heterogeneous catalysis, for example).

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“…Previous studies have shown that phase shifting between the forces and fluxes in a driven nonlinear system may be responsible for efficiency changes (3,10,25). We have analyzed the phase relationship of AG1 (Eq.…”

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Predictions of thermodynamic efficiency in a pumped biochemical reaction.

Hervagault

Lazar

Ross

1989

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

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We propose and analyze a possible experimental system for the investigation of the thermodynamic efficiency of generating biochemical gradients. We investigate the efficiency of a model pump that uses 6-phosphofructokinase (EC 2.7.1.11, an enzyme that exhibits highly nonlinear kinetics), chromatophores from Rhodobacter sphaeroides, and light to generate a biochemical gradient. We analyze the experimental system and an equivalent alternative configuration and show that the establishment and maintenance of a concentration gradient across a membrane is thermodynamically equivalent to the establishment and maintenance of a stationary state in a single-phase, isothermal, open, homogeneous reaction system. With a constant input of light, the system can exist in a stable node (a stable steady state), a stable focus (upon perturbation from its steady state, the system returns to its steady state with an oscillatory component), and a stable limit cycle (at steady state the system exhibits stable oscillations). We investigate the efficiency of the system with both steady and oscillatory light input and observe efficiency changes that depend upon the autonomous state ofthe system and the frequency and amplitude of the periodic light input. When the system is in a stable focus, an efficiency maximum is seen when the system is perturbed at its resonant frequency. When the system is in a stable limit cycle, efficiency increases are seen near the 1:3, 1:2, and 2:1 entrainment regions and an efficiency decrease is seen near the 1:1 entrainment region. We further calculate various contributions to the efficiency: the phase shift of the force and flux, the magnitude of the response to the perturbation, and changes in the average values of the force and flux during a perturbation. We show that all three changes contribute to the overall changes in efficiency, but increases and decreases in the average force make the largest contributions.We propose and analyze a possible experimental system for a study of the production of gradients of (bio)chemical species. The gradients may be used to do work in the surroundings of the system and the subject is closely related to the issue of efficiency of biological pumps. Prior articles have considered the thermodynamic efficiency of nonlinear model systems (1-3), combustion processes (4-7), the production of ATP in glycolysis (8)(9)(10)(11)(12)(13), and the thermodynamic efficiency of utilization of ATP in a simple model of a proton pump (14,15). In these studies, two modes of operation are investigated. In one mode, the system is in a stable attractor (a stationary state, either a node or a focus; a stable limit cycle) maintained by the constant influx of reactants; in the other mode, there are externally imposed oscillations of constraints such as the influx of ATP in the case of the proton pump, and of fuel influx in combustion. Nonlinearities in these systems far from equilibrium are sufficient to lead to variable dissipation and hence variable thermodynamic effih FIG. 1. The prop...

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Dependence of thermodynamic efficiency of proton pumps on frequency of oscillatory concentration of ATP.

Cited by 29 publications

References 20 publications

The strategy for coupling the RanGTP gradient to nuclear protein export

The strategy for coupling the RanGTP gradient to nuclear protein export

Changes in Mean Concentration, Phase Shifts, and Dissipation in a Forced Oscillatory Reaction

Predictions of thermodynamic efficiency in a pumped biochemical reaction.

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