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ATP synthase

The F-type proton ATP synthase is a ubiquitous rotating nanomachine that is formed from two coupled motors. The electrically driven motor, F0, a membrane-embedded proton turbine, is connected by two shafts with the chemically driven catalytic motor, F1 that protrudes into the water phase.


Proton transfer by rotary transporters. A scheme of proton transfer through F0. The figure is taken taken from [8]

Proton transfer though the ATP synthase

We have studied the properties of the proton transfer mechanism in the enzyme of Rhodobacter capsulatus. Relevantly, on tracing the partial steps of proton translocation by the F0F1-ATP-synthase, we have found that the native membrane vesicles, as isolated from bacterial cells, contain only one enzyme per vesicle at most. Therefore the measured kinetics of charge translocation by this enzyme reflected the turnover rates of single enzymes and were not ensemble-dependent. This approach opens the possibility to study any membrane translocator in a quasi-single-enzyme mode [10-12].


Schematic represantation of the inhibitor titration of electrochromic absorption transients under two different assumptions on the ATP synthase-contents in chromatophores. The figure is taken taken from [11]

Based on the available functional and structural information and the recent molecular dynamics simulations, we suggested a tentative scheme of a three-step proton transfer through the ATP synthase. According to this scheme, which takes into account the need to pay desolvation penalty, a proton, after getting into the surface located “proton trap” and being unable to pass further because of desolvation barrier, triggers a protein rearrangement accompanied by appearance ofnon-compensated electric charges in the membrane interior. The energetically favorable neutralization/removal of these charges is eventually coupled with the opening of an alternative exit for proton to the other side of the membrane [8].


Evolutionary history of the ATP synthases

The F-type ATP synthases show homology to another family of rotating machines, namely the V-type ATPases which are found in archaea and in eukaryotic membranes. By analyzing the homology pattern for different subunits of these related enzymes, we have put forward a scenario of their origin from primordial protein translocases [6].


Proposed evolution of the F- and V-type membrane ATPases. The figure is taken taken from [6]

Both F-type and V-type ATPases can translocate either protons or sodium ions. We have combined structural and phylogenetic analyses to clarify the evolutionary relation between the proton- and sodium-translocating ATPases. A comparison of the structures of the membrane-embedded oligomeric proteolipid rings of sodium-dependent F- and V-ATPases reveals nearly identical sets of amino acids involved in sodium binding. We show that the sodium-dependent ATPases are scattered among proton-dependent ATPases in both the F- and the V-branches of the phylogenetic tree. Barring convergent emergence of the same set of ligands in several lineages, these findings indicate that the use of sodium gradient for ATP synthesis is the ancestral modality of membrane bioenergetics and that the common ancestor of the F- and V-type ATPases contained a sodium-binding site [3-5].


Structure and evolutionary relationships of F-type and A/V-type ATPases, Structure of the sodium-binding site. The figure is taken from [3]

N-ATPases - a new family of rotary ATPases

An analysis of the distribution of the sodium-translocating ATPases/ATP synthases among microbial genomes identified an atypical form of the F1FO-type ATPase that is encoded in a number of phylogenetically diverse marine, halotolerant and pathogenic bacteria and in the archaea Methanosarcina barkeri and M. acetivorans,. In complete genomes, representatives of this form (referred to here as an N-ATPase) are always present as second copies, in addition to the typical proton-translocating ATP synthases. The N-ATPase is encoded by a highly conserved operon and its subunits cluster separately from the equivalent subunits of the typical F-type ATPases.The c subunits of N-ATPases usually carry a full set of sodium-binding residues, indicating that most of these enzymes are sodium-translocating ATPases that likely confer on their hosts the ability to extrude sodium ions. We suggest that N-ATPases are an early-diverging branch of membrane ion-translocating ATPases that, similarly to the eukaryotic V-type ATPases, are not involved in the synthesis of ATP. Thus, the Na-translocating common ancestor of all F-type ATPases apparently gave rise to two different families of ATPases: (i) the reversibleATPases/ATP synthases (‘genuine’F-ATPases) and (ii) ATP-driven ion pumps (N-ATPases)[2].


The figure is taken from [2]


1. Mulkidjanian, A.Y., M.Y. Galperin. 2010. Evolutionary origins of membrane proteins In: Structural Bioinformatics of Membrane Proteins (D. Frishman, Ed.), Springer, Wien, in press (Full text, pdf)

2. Dibrova, D.V., M.Y.Galperin, A.Y. Mulkidjanian, 2010. Characterization of the N-ATPase, a distinct, laterally transferred Na+-translocating form of the bacterial F-type membrane ATPase (Discovery Note). Bioinformatics, 26:1473-1476 (freely accessible at

3. Mulkidjanian, A.Y., M.Y. Galperin, E.V. Koonin. 2009. Co-evolution of membranes and membrane proteins, Trends Biochem. Sci. 34, 206-215. (Full text, pdf)

4. Mulkidjanian, A.Y., P. Dibrov, M.Y. Galperin. 2008. The past and present of the sodium energetics: May the sodium-motive force be with you, Biochim. Biophys. Acta, in press.(Full text, pdf)

5. Mulkidjanian, A.Y., M.Y. Galperin, K.S. Makarova, Y.I. Wolf, E.V. Koonin, 2008. Evolutionary primacy of sodium bioenergetics, Biol Direct 3 13.(Full text, pdf)

6. Mulkidjanian, A.Y., K.S. Makarova, M.Y. Galperin and E.V. Koonin. 2007. Inventing the dynamo machine: On the origin of the F-type and V-type membrane ATPases from membrane RNA/protein translocases, Nature Reviews Microbiology, 5:892-899.(Full text, pdf)

7. Feniouk, B.A, A. Rebecci, D.Giovanni, S. Anefors, A.Mulkidjanian, W.Junge, P.Turina, and B.A.Melandri. 2007. Met23Lys mutation in subunit gamma of FOF1-ATP synthase from Rhodobacter capsulatus impairs the activation of ATP hydrolysis by protonmotive force. Biochim. Biophys. Acta, 1767:1319-1330.(Full text, pdf)

8. Mulkidjanian, A.Y. 2006. Proton in the well and through the desolvation barrier, Biochim. Biophys. Acta, 1757: 415-427.(Full text, pdf)

9. Feniouk,B.A., A.Y.Mulkidjanian, and W.Junge. 2005. Proton slip in the ATP synthase of Rhodobacter capsulatus: induction, proton conduction, and nucleotide dependence. Biochim. Biophys. Acta 1706:184-194. (Full text, pdf)

10. Feniouk, B.A., M.A. Kozlova, D.A. Knorre, D.A. Cherepanov, A.Y. Mulkidjanian, and W. Junge. 2004. The proton driven rotor of ATP synthase: Ohmic conductance (10 fS), and absence of voltage gating. Biophys. J. 86: 4094-4109.(Full text, pdf)

11. Feniouk, B.A., D.A. Cherepanov, N.E. Voskoboynikova, A.Y. Mulkidjanian, and W. Junge. 2002. Chromatophore vesicles of Rhodobacter capsulatus contain on average one FOF1-ATP synthase each. Biophys. J. 82:1115-1122.(Full text, pdf)

12. Feniouk, BA, Cherepanov, DA, Junge, W, Mulkidjanian, AY. 2001. Coupling of proton flow to ATP synthesis in Rhodobacter capsulatus: FoF1-ATP synthase is absent from about half of chromatophores. Biochim. Biophys. Acta 1506, 189-203(Full text, pdf)

13. Cherepanov, D.A., A.Y. Mulkidjanian, and W. Junge. 1999. Transient accumulation of elastic energy in proton translocating ATP synthase. FEBS Lett. 449:1-6.(Full text, pdf)

14. Feniouk, B.A., Cherepanov, D.A., Junge, W., Mulkidjanian, A.Y. 1999. ATP-synthase of Rhodobacter capsulatus: coupling of proton flow through FO to reactions in F1 under ATP synthesis and slip conditions. FEBS Letters, 445, 409-414.(Full text, pdf)

15. Feniouk, B.A., W. Junge, and A.Y. Mulkidjanian. 1998. ATP-synthase of Rhodobacter capsulatus: Proton flow and ATP synthesis in response to light flashes. In Photosynthesis: Mechanisms and Effects. G. Garab, editor. Kluwer Academic Publishers, Dordrecht. 1679-1682.

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Letzte Änderung: 25.04.2019 Katrin Jahns