3zk2
From Proteopedia
Crystal structure of the sodium binding rotor ring at pH 8.7
Structural highlights
Function[ATPL_FUSNN] F(1)F(0) ATP synthase produces ATP from ADP in the presence of a proton or sodium gradient. F-type ATPases consist of two structural domains, F(1) containing the extramembraneous catalytic core and F(0) containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (By similarity). Key component of the F(0) channel; it plays a direct role in translocation across the membrane. A homomeric c-ring of between 10-14 subunits forms the central stalk rotor element with the F(1) delta and epsilon subunits (By similarity). Publication Abstract from PubMedThe 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 F(1)F(0)-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 c(1)(1) ring, solved by X-ray crystallography at 2.2 and 2.6 A 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. 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 O, Leone V, Matthies D, Cook GM, Faraldo-Gomez JD, Meier T PLoS Biol. 2013 Jun;11(6):e1001596. doi: 10.1371/journal.pbio.1001596. Epub 2013 , Jun 25. PMID:23824040[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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