Academic Journal
A new type of Na(+)-driven ATP synthase membrane rotor with a two-carboxylate ion-coupling motif.
| العنوان: | A new type of Na(+)-driven ATP synthase membrane rotor with a two-carboxylate ion-coupling motif. |
|---|---|
| المؤلفون: | Sarah Schulz, Marina Iglesias-Cans, Alexander Krah, Ozkan Yildiz, Vanessa Leone, Doreen Matthies, Gregory M Cook, José D Faraldo-Gómez, Thomas Meier |
| المصدر: | PLoS Biology, Vol 11, Iss 6, p e1001596 (2013) |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | Biology (General), QH301-705.5 |
| الوصف: | 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 F₁F₀-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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1544-9173 1545-7885 |
| Relation: | http://europepmc.org/articles/PMC3692424?pdf=render; https://doaj.org/toc/1544-9173; https://doaj.org/toc/1545-7885 |
| DOI: | 10.1371/journal.pbio.1001596 |
| URL الوصول: | https://doaj.org/article/314e0a549c3d4d76bf081a570d2bb2f2 |
| رقم الانضمام: | edsdoj.314e0a549c3d4d76bf081a570d2bb2f2 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15449173 15457885 |
|---|---|
| DOI: | 10.1371/journal.pbio.1001596 |