Structural basis for outer membrane lipopolysaccharide insertion

Haohao Dong, Quanju Xiang, Yinghong Gu, Zhongshan Wang, Neil G Paterson, Phillip J Stansfeld, Chuan He, Yizheng Zhang, Wenjian Wang, Changjiang Dong

Research output: Contribution to journalArticlepeer-review

204 Citations (Scopus)


Lipopolysaccharide (LPS) is essential for most Gram-negative bacteria and has crucial roles in protection of the bacteria from harsh environments and toxic compounds, including antibiotics. Seven LPS transport proteins (that is, LptA-LptG) form a trans-envelope protein complex responsible for the transport of LPS from the inner membrane to the outer membrane, the mechanism for which is poorly understood. Here we report the first crystal structure of the unique integral membrane LPS translocon LptD-LptE complex. LptD forms a novel 26-stranded β-barrel, which is to our knowledge the largest β-barrel reported so far. LptE adopts a roll-like structure located inside the barrel of LptD to form an unprecedented two-protein 'barrel and plug' architecture. The structure, molecular dynamics simulations and functional assays suggest that the hydrophilic O-antigen and the core oligosaccharide of the LPS may pass through the barrel and the lipid A of the LPS may be inserted into the outer leaflet of the outer membrane through a lateral opening between strands β1 and β26 of LptD. These findings not only help us to understand important aspects of bacterial outer membrane biogenesis, but also have significant potential for the development of novel drugs against multi-drug resistant pathogenic bacteria.
Original languageEnglish
Pages (from-to)52-6
Number of pages5
Issue number7507
Early online date18 Jun 2014
Publication statusPublished - 3 Jul 2014


  • Bacterial Outer Membrane Proteins
  • Cell Membrane
  • Cell Wall
  • Crystallography, X-Ray
  • Lipopolysaccharides
  • Models, Molecular
  • Multiprotein Complexes
  • Protein Binding
  • Protein Structure, Secondary
  • Salmonella typhimurium
  • Structure-Activity Relationship

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