Dataset Information

Molecular insights into the capsular polysaccharide transporter Wza-Wzc complex

ABSTRACT: Capsular polysaccharides (CPS), which form the protective outer capsule surrounding many Gram-negative bacterial pathogens, are critical virulence determinants. Their biosynthesis is primarily carried out via the conserved Wzx/Wzy-dependent pathway. In Escherichia coli, Group 1 CPS transport through the bacterial envelope is thought to be mediated by the Wza-Wzc complex. In this study, we present the first structural characterization of the complete Wza-Wzc complex from E. coli K12, determined using single-particle cryogenic electron microscopy. The structure revealed an elongated, continuous channel spanning the entire envelope, which is crucial for efficient CPS secretion, as supported by mutagenesis studies. Multiple structural snapshots of the ADP-bound Wza-Wzc complex captured intermediate conformations of the double membrane assembly, highlighting its remarkable intrinsic dynamics. In-depth analysis of the isolated Wza translocon and Wzc co-polymerase, revealed new mechanistic details of both complex formation and CPS transport. Importantly, we identified the jellyroll domain of Wzc as a previously unrecognized CPS-binding module, likely guiding CPS repeat units into a proposed Wzc-Wzy polymerization platform. Collectively, these findings provide new structural and functional insights into CPS synthesis and transport, advancing our understanding of bacterial capsule formation and virulence mechanisms.

INSTRUMENT(S):

ORGANISM(S): Escherichia Coli

SUBMITTER: Lothar Jaensch

LAB HEAD: Lothar Jänsch

PROVIDER: PXD064872 | Pride | 2026-02-23

REPOSITORIES: Pride

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			Action	DRS
	X1167_S41_1_1uL_2ng.raw	Raw
	X1168_S41_2_1uL_2ng.raw	Raw
	X1169_S41_3_1uL_2ng.raw	Raw
	X1203_S41_1_Phospho_1uL_1ng.raw	Raw
	X1204_S41_2_Phospho_1uL_1ng.raw	Raw

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

Yuan Biao B Sieben Christian C Raj Prateek P Rietschel Tina T Hennell James Rory R Gatzemeier Anja A Jänsch Lothar L Marlovits Thomas C TC Heinz Dirk W DW

Nature communications 20260205 1

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 do ...[more]

PMID: 41644548

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