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

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 system. EPSs have critical roles in bacterial colonization of surfaces, such as epithelia and medical implants; in addition some EPSs have important industrial and biomedical applications in their own right. Here we describe the 2.26 A 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 alpha-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.     

Tumor microenvironment: becoming sick of Myc

Several years ago, we described Myc as “the oncogene from hell”, since evidence had just emerged that Myc, aside from being responsible for cell-cycle progression and tumor expansion, was also able to induce genomic instability in culture, wreaking havoc in tumor cells and accelerating tumor progression (Soucek and Evan, Cancer Cell 1:406–408, 2002; Vafa et al., Mol Cell 9:1031–1044, 2002). In this review, we discuss recent publications that expand Myc’s evil armory to include coordination of the crosstalk between tumor and microenvironment. Indeed, endogenous Myc, acting as a client for upstream oncogenic lesions, instructs the tumor stroma, engages a complex inflammatory response and induces angiogenesis, thus allowing the tumor to thrive. This is highly topical in light of the fact that Hanahan and Weinberg have recently redefined the hallmarks of cancer and pointed out that genomic instability and inflammation are essential for both their acquisition and development (Hanahan and Weinberg, Cell 144:646–674, 2011). Myc, it seems, is behind it all.