title: Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase.
abstract: NADH oxidation in the respiratory chain is coupled to ion translocation across the membrane to build up an electrochemical gradient. The sodium-translocating NADH:quinone oxidoreductase (Na(+)-NQR), a membrane protein complex widespread among pathogenic bacteria, consists of six subunits, NqrA, B, C, D, E and F. To our knowledge, no structural information on the Na(+)-NQR complex has been available until now. Here we present the crystal structure of the Na(+)-NQR complex at 3.5 Å resolution. The arrangement of cofactors both at the cytoplasmic and the periplasmic side of the complex, together with a hitherto unknown iron centre in the midst of the membrane-embedded part, reveals an electron transfer pathway from the NADH-oxidizing cytoplasmic NqrF subunit across the membrane to the periplasmic NqrC, and back to the quinone reduction site on NqrA located in the cytoplasm. A sodium channel was localized in subunit NqrB, which represents the largest membrane subunit of the Na(+)-NQR and is structurally related to urea and ammonia transporters. On the basis of the structure we propose a mechanism of redox-driven Na(+) translocation where the change in redox state of the flavin mononucleotide cofactor in NqrB triggers the transport of Na(+) through the observed channel.
authors.affiliation: Department of Microbiology, Garbenstrasse 30, University of Hohenheim, 70599 Stuttgart, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Steuber
authors.affiliation: 1] Institute for Neuropathology, University of Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany [2] Hermann-Staudinger-Graduate school, University of Freiburg, Hebelstrasse 27, 79104 Freiburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Vohl
authors.affiliation: Institute for Neuropathology, University of Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany.
authors.forename: Marco S
authors.initials: MS
authors.lastname: Casutt
authors.affiliation: Department of Microbiology, Garbenstrasse 30, University of Hohenheim, 70599 Stuttgart, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vorburger
authors.affiliation: Department of Biology, University of Konstanz, Universitätsstrasse 10, 78457 Konstanz, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Diederichs
authors.affiliation: Institute for Neuropathology, University of Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Fritz
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D005420:Flavoproteins / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D008958:Models, Molecular; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry*; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D012964:Sodium / Q000737:chemistry*; D015222:Sodium Channels / Q000737:chemistry; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D005420:Flavoproteins; D021122:Protein Subunits; D015222:Sodium Channels; D012964:Sodium; D007501:Iron; D016660:NAD(P)H Dehydrogenase (Quinone)