In Gram-negative bacteria, the components of the outer membrane are synthesized in the cytoplasm or the inner membrane and must therefore traverse the inner membrane and the periplasm on the way to their final destination. Lipopolysaccharide molecules (LPS) are an essential component of the bacterial outer membrane and consist of a hydrophobic membrane anchor (lipid A) and an oligosaccharide core region that can be extended in some bacteria by a repeating oligosaccharide, the O-antigen. An outer membrane protein, which probably forms a ß-barrel, is required for the appearance of LPS at the bacterial cell surface. This protein is known as Imp (increased membrane permeability) or OstA (organic solvent tolerance) because Escherichia coli strains expressing mutant versions of this protein showed altered membrane permeability. LptD is an essential OMP that mediates the final transport of LPS to outer leaflet. LptD forms a novel 26-stranded ß-barrel, which is to our knowledge one of the largest ß-barrel reported so far. LptE adopts a roll-like structure located inside the barrel of LptD to form an unprecedented two-protein 'barrel and plug' architecture. The structure, molecular dynamics simulations and functional assays suggest that the hydrophilic O-antigen and the core oligosaccharide of the LPS may pass through the barrel and the lipid A of the LPS may be inserted into the outer leaflet of the outer membrane through a lateral opening between strands ß1 and ß26 of LptD.

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