# Molecular insights into the capsular polysaccharide transporter Wza-Wzc complex

## TL;DR

This study reveals the structure and function of a bacterial complex involved in transporting protective sugar molecules, shedding light on how bacteria form their protective capsule.

## Contribution

The study provides the first complete cryo-EM structure of the Wza-Wzc complex and reveals its dynamic assembly and CPS transport mechanism.

## Key findings

- The Wza-Wzc complex forms an elongated channel spanning the bacterial envelope for CPS secretion.
- The jellyroll domain of Wzc acts as a CPS-binding module, guiding sugar units into a polymerization platform.
- Structural snapshots show the complex's dynamic conformations during CPS transport.

## Abstract

Capsular polysaccharides (CPS) are key virulence determinants, constituting the protective capsule that surrounds bacterial pathogens. Here, we present the complete cryo-EM structure of Gram-negative bacterial CPS secretion machinery formed by the E. coli K12 Wza-Wzc complex. The structure reveals an elongated, continuous channel spanning the entire envelope that facilitates CPS secretion. Multiple structural snapshots of the ADP-bound Wza-Wzc complex capture intermediate conformations of the double membrane assembly, highlighting its remarkable intrinsic dynamics. In-depth analysis of the isolated Wza translocon and Wzc co-polymerase, reveals mechanistic details of both complex formation and CPS transport. We further uncover the jellyroll domain of Wzc as a CPS-binding module, likely guiding CPS repeat units into a proposed Wzc-Wzy polymerization platform. Collectively, this work provides structural and functional insights into CPS synthesis and transport, advancing our understanding of bacterial capsule formation and virulence mechanisms.

Capsular polysaccharides are bacterial virulence factors, yet their transport mechanism remains unclear. Here, the authors reveal the structure and dynamics of the Wza–Wzc complex, uncovering how a trans-envelope channel assembles to guide capsular polysaccharide synthesis and export.