Sensitivity analysis of the proton transport through the half-channels of F0F1-ATP synthase to transmembrane potential changes


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Abstract

Introduction. ATP is one of the most frequently updated molecules in the organism. The presence of a transmembrane gradient of H+ electrochemical potential is a crucial condition for the synthesis of ATP using FFfATP synthase enzyme, which affects proton transport through the Fo factor. The aim of the study was to evaluate the effect of the transmembrane potential on the proton transport parameters through the inlet halfchannel of FFfATP synthase taking into account its possible spatial polymorphism. Methods. A combined approach is used for proton motion modeling. Probability of proton transfer is determined by a quantum-mechanical approach of one-dimensional motion and the problem of proton transport through a sequence of charged centers in the halfchannel is considered in the framework of the stochastic approach. Results. The values of the proton transport times obtained in the model of 10-10-10-s s are in a good accordance with the experimental estimates of the ion transfer time in various biological objects for the certain physicochemical characteristics. In the range of physiological values of the membrane potential, the time was almost unchanged. Linear dependence between the transport time and the membrane potential was established for the transmembrane oriented 1C17 pdb-structure, which led to a time increase by 11% without the potential. In case of the laterally oriented 5T4O pdb-structure the transport became slower, however, no apparent linear dependence has been identified. Conclusion. The results obtained in this work can be used to evaluate the proton current through the half-channel and the contribution of transport time to the total time of ATP synthesis. In addition, proton transport adaptability analysis enlightens the additional vulnerability points of the catalytic cycle of FFfATP synthase in case of integrality problems and membrane characteristics changes.

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L. A Ivontsin

Research Institute of Cytochemistry and Molecular Pharmacology

Email: ivontsin@icmph.ru

E. V Mashkovtseva

Research Institute of Cytochemistry and Molecular Pharmacology

Ya. R Nartsissov

Research Institute of Cytochemistry and Molecular Pharmacology

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