Many bacteria possess an external polysaccharide 'capsule' that helps them evade the host immune system and colonize surfaces. As a point of contact between host and pathogen, the capsule is a potential target for vaccines and other therapies. The three-dimensional structure of Wza, a protein responsible for exporting a capsular polysaccharide in Escherichia coli, has now been determined. Most of the protein is located in the periplasm, the space between the inner plasma membrane and the outer cellular membrane, and the protein contains a large central cavity through which the polysaccharide is transported. The X-ray crystal structure of the 340-kDa octamer of Wza, essential for group 1 capsule export in Escherichia coli, is determined. A large portion of Wza is located in the periplasm and the protein contains a large central cavity, through which capsular polysaccharides are translocated. Many types of bacteria produce extracellular polysaccharides (EPSs). Some are secreted polymers and show only limited association with the cell surface, whereas others are firmly attached to the cell surface and form a discrete structural layer, the capsule, which envelopes the cell and allows the bacteria to evade or counteract the host immune system1. EPSs have critical roles in bacterial colonization of surfaces2, such as epithelia and medical implants; in addition some EPSs have important industrial and biomedical applications in their own right3. Here we describe the 2.26 Å resolution structure of the 340 kDa octamer of Wza, an integral outer membrane lipoprotein, which is essential for group 1 capsule export in Escherichia coli. The transmembrane region is a novel α-helical barrel. The bulk of the Wza structure is located in the periplasm and comprises three novel domains forming a large central cavity. Wza is open to the extracellular environment but closed to the periplasm. We propose a route and mechanism for translocation of the capsular polysaccharide. This work may provide insight into the export of other large polar molecules such as DNA and proteins.

Wza the translocon for E. coli capsular polysaccharides defines a new class of membrane protein