3ZK1

Crystal structure of the sodium binding rotor ring at pH 5.3

Summary for 3ZK1

• Entry DOI: 10.2210/pdb3zk1/pdb
• Related: 3ZK2
• Descriptor: ATP SYNTHASE SUBUNIT C, SODIUM ION, DECYL-BETA-D-MALTOPYRANOSIDE, ... (6 entities in total)
• Functional Keywords: membrane protein, atp synthase, rotor ring
• Biological source: FUSOBACTERIUM NUCLEATUM
• Cellular location: Cell inner membrane; Multi-pass membrane protein (By similarity): Q8RGD7
• Total number of polymer chains: 22
• Total formula weight: 208085.95

Authors

Schulz, S.,Meier, T.,Yildiz, O. (deposition date: 2013-01-21, release date: 2013-05-29, Last modification date: 2023-12-20)

Primary citation

Schulz, S.,Iglesias-Cans, M.,Krah, A.,Yildiz, O.,Leone, V.,Matthies, D.,Cook, G.M.,Faraldo-Gomez, J.D.,Meier, T.
A New Type of Na(+)-Driven ATP Synthase Membrane Rotor with a Two-Carboxylate Ion-Coupling Motif.
Plos Biol., 11:01596-, 2013

PubMed 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 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.

PubMed: 23824040
DOI: 10.1371/JOURNAL.PBIO.1001596

Experimental method

X-RAY DIFFRACTION (2.2 Å)