Structural Basis of Lipopolysaccharide Transport

The role of Lipopolysaccharides in Gram-negative bacteria is critical for the bacterial survival and their resistance to antibiotics. A most intriguing step in the biosynthesis is a trans-bilayer movement which brings the Lipopolysaccharides from the leaflet of the inner membrane to the periplasmic leaflet. Such a mechanism involving flippases has remained elusive. Using single particle cryo-EM, the structure of lipid nano-discs embedded in an ATP-binding cassette transporter (MsbA) has been established in three functional steps. This study uncovers the structural basis for Lipopolysaccharides transport as a result of a so-called "trap and flip" model and paves the way for structural characterization of many other lipid flippases.