Molecular insights into the capsular polysaccharide transporter Wza-Wzc complex

Abstract

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.