3ZK2

Crystal structure of the sodium binding rotor ring at pH 8.7

3ZK2 の概要

• エントリーDOI: 10.2210/pdb3zk2/pdb
• 関連するPDBエントリー: 3ZK1
• 分子名称: ATP SYNTHASE SUBUNIT C, SODIUM ION, DECYL-BETA-D-MALTOPYRANOSIDE, ... (4 entities in total)
• 機能のキーワード: membrane protein, hydrolase, rotor ring
• 由来する生物種: FUSOBACTERIUM NUCLEATUM
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 206710.23

構造登録者

Schulz, S.,Meier, T.,Yildiz, O. (登録日: 2013-01-21, 公開日: 2013-05-29, 最終更新日: 2023-12-20)

主引用文献

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:e1001596-e1001596, 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

実験手法

X-RAY DIFFRACTION (2.63 Å)