Molecular and functional properties of the Na+ -translocating NADH:quinone oxidoreductase (Na+ -NQR) from Vibrio cholerae
Final Report Abstract
The bacterium Vibrio cholerae causes cholera, a severe diarrhoeal disease that affects up to 3.5 million people a year. We gained new insights into how the bacterium produces energy by elucidating the structure and function of its energy-production machinery. Like many other organisms, V. cholerae generates energy by way of the so-called respiratory chain along which electrons are transferred by a series of proteins. These proteins are power plants acting as pumps driven by electron transfer. The respiratory chain of V. cholerae includes a sodium ion pump that energizes the cellular battery which in turn drives many other processes important for survival of the pathogen. This power plant is the Achilles heel of the cholera pathogen. Besides V. cholerae, the sodium pump is prevalent among many pathogenic bacteria. Notably, the pump is completely different from power plants operating in humans. This increases the chance to specifically interfere with the bacterial sodium pump without inactivating human metabolism. The results of our project gave us new insights into biochemical energy production of bacteria in general, but also represent the basis to develop new antibiotics that target V. cholerae and other pathogens relying on the sodium pump for energy production. Der Choleraerreger setzt auf alternative Energie: http://www.laborundmore.de/archive/177,503602/BioBiotech/Der-Choleraerreger-setzt-auf-alternative-Energie.html Riesenkraftwerk des Cholera-Erregers entschlüsselt: http://www.uniklinik-freiburg.de/presse/pressemitteilungen/archiv-2014/detailansicht/presse/357.html?tx_aspresse_pi1[backLink]=1782&cHash=9d2aa93e8047d29e5dd661f1c845eea0 „Zell-Kraftwerk“ des Choleraerregers; von der Struktur zu neuen Antibiotika: http://biopro.de/magazin/index.html?lang=de&artikelid=/artikel/10347/index.html
Publications
- (2013) NMR reveals double occupancy of quinonetype ligands in the catalytic quinone binding site of the Na+-translocating NADH:quinone oxidoreductase from Vibrio cholerae. J. Biol. Chem., 288:30597-30606
Nedielkov, R., Steffen, W., Steuber, J., Möller, H.
(See online at https://doi.org/10.1074/jbc.M112.435750) - (2014) Central role of the Na+ - translocating NADH:quinone oxidoreductase (Na+ -NQR) in sodium bioenergetics of Vibrio cholerae. Biol. Chem., 395, 1389-1399
Steuber, J., Halang, P., Vorburger, T., Steffen, W., Vohl, G., Fritz, G.
(See online at https://doi.org/10.1515/hsz-2014-0204) - (2014) Continuous fluorescence based measurement of redox driven sodium ion translocation. Anal. Biochem., 459:53-55
Muras, V., Claussen, B., Karuppasamy, M., Schaffitzel, C., Steuber, J.
(See online at https://doi.org/10.1016/j.ab.2014.05.012) - (2014) Crystallization and preliminary analysis of the subunits NqrA and NqrC of the Na+ -translocating NADH:ubiquinone oxidoreductase from Vibrio cholerae. Acta Cryst. F, 70, 987–992
Vohl, G., Nedielkov, R., Claussen, B., Casutt, M., Vorburger, T., Diederichs, K., Möller, H.M., Steuber, J., Fritz, G.
(See online at https://doi.org/10.1107/S2053230X14009881) - (2014) Roles of the sodium-translocating NADH-quinone oxidoreductase (NQR) on Vibrio cholerae metabolism, motility and osmotic stress resistance. PLOSone, 9(5): e97083
Minato, Y., Fassio, S.R., Kirkwood, J.S., Halang, P., Quinn, M.J., Faulkner, W.J., Aagesen, A.M., Steuber, J., Stevens, J.F., Häse, C.C.
(See online at https://doi.org/10.1371/journal.pone.0097083) - (2014) Structure of the V.cholerae Na+-pumping NADH:quinone oxidoreductase. Nature, 516: 62-67
Steuber, J., Vohl, G., Casutt, M.S., Vorburger, T., Diederichs, K., Fritz, G.
(See online at https://doi.org/10.1038/nature14003) - (2015) The structure of Na+ -translocating NADH:ubiquinone oxidoreductase of Vibrio cholerae: implications on coupling between electron transfer and Na+ transport. Biol Chem., 396:1015-103o
Steuber, J., Vohl G., Muras V., Toulouse C., Claußen B., Vorburger T., Fritz G.
(See online at https://doi.org/10.1515/hsz-2015-0128) - (2016) Role of the Na+-translocating NADH:quinone oxidoreductase in voltage generation and Na+ extrusion in Vibrio cholerae. Biochim Biophys Acta (Bioenergetics), 1857: 473-478
Vorburger, T.; Nedielkov, R.; Brosig, A.; Bok, E.; Schunke, E.; Steffen, W.; Mayer, S.; Götz, F.; Möller, H.M.; Steuber, J.
(See online at https://doi.org/10.1016/j.bbabio.2015.12.010) - “Sodium as Coupling Cation in Respiratory Energy Conversion” in: The Alkali Metal Ions: Their Role for Life, Vol. 16 of Metal Ions in Life Sciences, Eds A. Sigel, H. Sigel, R.K.O. Sigel, Springer International, Cham, Switzerland, 2016, p. 349-385
Fritz, G., Steuber, J.
