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  A New Type of Na+-Driven ATP Synthase Membrane Rotor with a Two-Carboxylate Ion-Coupling Motif

Schulz, S., Iglesias-Cans, M., Krah, A., Yildiz, Ö., Leone, V., Matthies, D., et al. (2013). A New Type of Na+-Driven ATP Synthase Membrane Rotor with a Two-Carboxylate Ion-Coupling Motif. PLoS Biology, 11(6): e1001596, pp. 1-12. doi:10.1371/journal.pbio.1001596.

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 Creators:
Schulz, Sarah1, Author           
Iglesias-Cans, Marina2, Author
Krah, Alexander3, Author           
Yildiz, Özkan1, Author           
Leone, Vanessa3, Author           
Matthies, Doreen1, Author           
Cook, Gregory M.2, Author
Faraldo-Gómez, José D.3, 4, Author           
Meier, Thomas1, 4, Author           
Affiliations:
1Department of Structural Biology, Max Planck Institute of Biophysics, Max Planck Society, ou_2068291              
2 Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand , ou_persistent22              
3Max Planck Research Group of Theoretical Molecular Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068295              
4Cluster of Excellence ‘‘Macromolecular Complexes,’’ Goethe University of Frankfurt, Frankfurt am Main, Germany, ou_persistent22              

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 Abstract: The anaerobic bacterium Fusobacterium nucleatum uses glutamate decarboxylation to generate a transmembrane gradient of Na+. Here, we demonstrate that this ion-motive force is directly coupled to ATP synthesis, via an F1Fo-ATP synthase with a novel Na+ recognition motif, shared by other human pathogens. Molecular modeling and free-energy simulations of the rotary element of the enzyme, the c-ring, indicate Na+ specificity in physiological settings. Consistently, activity measurements showed Na+ stimulation of the enzyme, either membrane-embedded or isolated, and ATP synthesis was sensitive to the Na+ ionophore monensin. Furthermore, Na+ has a protective effect against inhibitors targeting the ion-binding sites, both in the complete ATP synthase and the isolated c-ring. Definitive evidence of Na+ coupling is provided by two identical crystal structures of the c11 ring, solved by X-ray crystallography at 2.2 and 2.6 Å resolution, at pH 5.3 and 8.7, respectively. Na+ ions occupy all binding sites, each coordinated by four amino acids and a water molecule. Intriguingly, two carboxylates instead of one mediate ion binding. Simulations and experiments demonstrate that this motif implies that a proton is concurrently bound to all sites, although Na+ alone drives the rotary mechanism. The structure thus reveals a new mode of ion coupling in ATP synthases and provides a basis for drug-design efforts against this opportunistic pathogen.

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Language(s): eng - English
 Dates: 2013-02-052013-05-162013-06-25
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1371/journal.pbio.1001596
PMID: 23824040
PMC: 3692424
 Degree: -

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Title: PLoS Biology
  Other : PLoS Biol.
Source Genre: Journal
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Publ. Info: San Francisco, California, US : Public Library of Science
Pages: - Volume / Issue: 11 (6) Sequence Number: e1001596 Start / End Page: 1 - 12 Identifier: ISSN: 1544-9173
CoNE: https://pure.mpg.de/cone/journals/resource/111056649444170