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.
Yuan et al. (2026) studied this question.