Imperial College London
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ProfessorThomasMeier

Faculty of Natural Sciences, Department of Life Sciences

Visiting Professor
 
 
 
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Contact

 

t.meier Website

 
 
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Location

 

501Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Schulz:2013:10.1371/journal.pbio.1001596,
author = {Schulz, S and Iglesias-Cans, M and Krah, A and Yildiz, Ö and Leone, V and Matthies, D and Cook, GM and Faraldo-Gómez, JD and Meier, T},
doi = {10.1371/journal.pbio.1001596},
journal = {PLOS Biology},
title = {A New Type of Na+-Driven ATP Synthase Membrane Rotor with a Two-Carboxylate Ion-Coupling Motif},
url = {http://dx.doi.org/10.1371/journal.pbio.1001596},
volume = {11},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Schulz,S
AU  - Iglesias-Cans,M
AU  - Krah,A
AU  - Yildiz,Ö
AU  - Leone,V
AU  - Matthies,D
AU  - Cook,GM
AU  - Faraldo-Gómez,JD
AU  - Meier,T
DO  - 10.1371/journal.pbio.1001596
PY  - 2013///
SN  - 1545-7885
TI  - A New Type of Na+-Driven ATP Synthase Membrane Rotor with a Two-Carboxylate Ion-Coupling Motif
T2  - PLOS Biology
UR  - http://dx.doi.org/10.1371/journal.pbio.1001596
UR  - http://hdl.handle.net/10044/1/40440
VL  - 11
ER  -
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