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Structural basis for outer membrane lipopolysaccharide insertion

Author

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  • Haohao Dong

    (Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK
    Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK)

  • Quanju Xiang

    (Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK
    College of Resource and Environment Science, Sichuan Agriculture University)

  • Yinghong Gu

    (Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK)

  • Zhongshan Wang

    (Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK
    Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK
    College of Life Sciences, Sichuan University)

  • Neil G. Paterson

    (Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK)

  • Phillip J. Stansfeld

    (University of Oxford, South Parks Road, Oxford OX1 3QU, UK)

  • Chuan He

    (Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK
    School of Electronics and Information, Wuhan Technical College of Communications, No.6 Huangjiahu West Road, Hongshan District, Wuhan, Hubei 430065, China)

  • Yizheng Zhang

    (College of Life Sciences, Sichuan University)

  • Wenjian Wang

    (the First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, China)

  • Changjiang Dong

    (Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK)

Abstract

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.

Suggested Citation

  • Haohao Dong & Quanju Xiang & Yinghong Gu & Zhongshan Wang & Neil G. Paterson & Phillip J. Stansfeld & Chuan He & Yizheng Zhang & Wenjian Wang & Changjiang Dong, 2014. "Structural basis for outer membrane lipopolysaccharide insertion," Nature, Nature, vol. 511(7507), pages 52-56, July.
  • Handle: RePEc:nat:nature:v:511:y:2014:i:7507:d:10.1038_nature13464
    DOI: 10.1038/nature13464
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    Cited by:

    1. Dawei Sun & Kelly M. Storek & Dimitry Tegunov & Ying Yang & Christopher P. Arthur & Matthew Johnson & John G. Quinn & Weijing Liu & Guanghui Han & Hany S. Girgis & Mary Kate Alexander & Austin K. Murc, 2024. "The discovery and structural basis of two distinct state-dependent inhibitors of BamA," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Yiying Yang & Haoxiang Chen & Robin A. Corey & Violette Morales & Yves Quentin & Carine Froment & Anne Caumont-Sarcos & Cécile Albenne & Odile Burlet-Schiltz & David Ranava & Phillip J. Stansfeld & Ju, 2023. "LptM promotes oxidative maturation of the lipopolysaccharide translocon by substrate binding mimicry," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Yun Meng & Lijie Chen & Yang Chen & Jieyun Shi & Zheng Zhang & Yiwen Wang & Fan Wu & Xingwu Jiang & Wei Yang & Li Zhang & Chaochao Wang & Xianfu Meng & Yelin Wu & Wenbo Bu, 2022. "Reactive metal boride nanoparticles trap lipopolysaccharide and peptidoglycan for bacteria-infected wound healing," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Mathieu Botte & Dongchun Ni & Stephan Schenck & Iwan Zimmermann & Mohamed Chami & Nicolas Bocquet & Pascal Egloff & Denis Bucher & Matilde Trabuco & Robert K. Y. Cheng & Janine D. Brunner & Markus A. , 2022. "Cryo-EM structures of a LptDE transporter in complex with Pro-macrobodies offer insight into lipopolysaccharide translocation," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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