Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase

NADH oxidation in the respiratory chain is coupled to ion translocation across the membrane to build up an electrochemical gradient. The sodium -translocattng NADH:quinone oxidoreductase (Na+-NQR), amembrane protein complex widespread among pathogenic bacteria' consists of six subunits, NqrA, B, C, D, E and F. 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 angstrom resolution. The arrangement of cofactors both at the cytoplasmic and the periplastnic 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 petiplasmic NqrC, and back to the qui none reduction site on NqrA located in the cytoplasm. A soditun channel was localized in subunit Nqr13, 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.