A low-resolution structure of the Na(+)-translocating NADH:ubiquinone oxidoreductase from the human pathogen Vibrio cholerae was determined by ab initio phasing and independently confirmed by electron microscopy. This multi-subunit membrane-protein complex (molecular weight 210 kDa) generates an Na(+) gradient that is essential for substrate uptake, motility, pathogenicity and efflux of antibiotics. The obtained 16 Å resolution electron density-map revealed an asymmetric particle with a central region of low electron density and a putative detergent region, and allowed the identification of the transmembrane regions of the complex.