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Structural basis for outer membrane lipopolysaccharide insertion
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Dong, Haohao, Xiang, Quanju, Gu, Yinghong, Wang, Zhongshan, Paterson, Neil G., Stansfeld, Phillip J., He, Chuan, Zhang, Yizheng, Wang, Wenjian and Dong, Changjiang (2014) Structural basis for outer membrane lipopolysaccharide insertion. Nature, 511 (7507). pp. 52-56. doi:10.1038/nature13464 ISSN 0028-0836.
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WRAP-Structural-basis-outer-membrane-lipopolysaccharide-insertion-Stansfeld-2014.pdf - Accepted Version - Requires a PDF viewer. Download (1073Kb) | Preview |
Official URL: http://dx.doi.org/10.1038/nature13464
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.
Item Type: | Journal Article | |||||||||
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Subjects: | Q Science > QP Physiology Q Science > QR Microbiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
Library of Congress Subject Headings (LCSH): | Endotoxins, Gram-negative bacteria, Membranes (Biology) | |||||||||
Journal or Publication Title: | Nature | |||||||||
Publisher: | Nature Publishing | |||||||||
ISSN: | 0028-0836 | |||||||||
Official Date: | 3 July 2014 | |||||||||
Dates: |
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Volume: | 511 | |||||||||
Number: | 7507 | |||||||||
Page Range: | pp. 52-56 | |||||||||
DOI: | 10.1038/nature13464 | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Access rights to Published version: | Restricted or Subscription Access | |||||||||
Date of first compliant deposit: | 11 November 2019 | |||||||||
Date of first compliant Open Access: | 11 November 2019 | |||||||||
RIOXX Funder/Project Grant: |
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