| Structural highlights
9g95 is a 2 chain structure with sequence from Escherichia coli and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.8Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
WZXE_ECOLI Mediates the transbilayer movement of Und-PP-GlcNAc-ManNAcA-Fuc4NAc (lipid III) from the inner to the outer leaflet of the cytoplasmic membrane during the assembly of enterobacterial common antigen (ECA). Required for the assembly of the phosphoglyceride-linked form of ECA (ECA(PG)) and the water-soluble cyclic form of ECA (ECA(CYC)). Could also mediate the translocation of Und-PP-GlcNAc.[1] [2]
Publication Abstract from PubMed
The enterobacterial common antigen (ECA) is conserved in Gram-negative bacteria of the Enterobacterales order although its function is debated. ECA biogenesis depends on the Wzx/Wzy-dependent strategy whereby the newly synthesized lipid-linked repeat units, lipid III, are transferred across the inner membrane by the lipid III flippase WzxE. WzxE is part of the Wzx family and required in many glycan assembly systems, but an understanding of its molecular mechanism is hindered due to a lack of structural evidence. Here, we present the first X-ray structures of WzxE from Escherichia coli in complex with nanobodies. Both inward- and outward-facing conformations highlight two pairs of arginine residues that move in a reciprocal fashion, enabling flipping. One of the arginine pairs coordinated to a glutamate residue is essential for activity along with the C-terminal arginine rich tail located close to the entrance of the lumen. This work helps understand the translocation mechanism of the Wzx flippase family.
Structure of WzxE the lipid III flippase for Enterobacterial Common Antigen polysaccharide.,Le Bas A, Clarke BR, Teelucksingh T, Lee M, El Omari K, Giltrap AM, McMahon SA, Liu H, Beale JH, Mykhaylyk V, Duman R, Paterson NG, Ward PN, Harrison PJ, Weckener M, Pardon E, Steyaert J, Liu H, Quigley A, Davis BG, Wagner A, Whitfield C, Naismith JH Open Biol. 2025 Jan;15(1):240310. doi: 10.1098/rsob.240310. Epub 2025 Jan 8. PMID:39772807[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rick PD, Barr K, Sankaran K, Kajimura J, Rush JS, Waechter CJ. Evidence that the wzxE gene of Escherichia coli K-12 encodes a protein involved in the transbilayer movement of a trisaccharide-lipid intermediate in the assembly of enterobacterial common antigen. J Biol Chem. 2003 May 9;278(19):16534-42. PMID:12621029 doi:10.1074/jbc.M301750200
- ↑ Kajimura J, Rahman A, Rick PD. Assembly of cyclic enterobacterial common antigen in Escherichia coli K-12. J Bacteriol. 2005 Oct;187(20):6917-27. PMID:16199561 doi:10.1128/JB.187.20.6917-6927.2005
- ↑ Le Bas A, Clarke BR, Teelucksingh T, Lee M, El Omari K, Giltrap AM, McMahon SA, Liu H, Beale JH, Mykhaylyk V, Duman R, Paterson NG, Ward PN, Harrison PJ, Weckener M, Pardon E, Steyaert J, Liu H, Quigley A, Davis BG, Wagner A, Whitfield C, Naismith JH. Structure of WzxE the lipid III flippase for Enterobacterial Common Antigen polysaccharide. Open Biol. 2025 Jan;15(1):240310. PMID:39772807 doi:10.1098/rsob.240310
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