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Nature. 2014 Jul 3;511(7507):52-6. doi: 10.1038/nature13464. Epub 2014 Jun 18.

Structural basis for outer membrane lipopolysaccharide insertion.

Author information

1
1] Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK [2] Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.
2
1] Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK [2] Department of Microbiology, College of Resource and Environment Science, Sichuan Agriculture University, Yaan 625000, China.
3
Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
4
1] Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK [2] Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK [3] College of Life Sciences, Sichuan University, Chengdu 610065, China.
5
Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.
6
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
7
1] Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK [2] School of Electronics and Information, Wuhan Technical College of Communications, No.6 Huangjiahu West Road, Hongshan District, Wuhan, Hubei 430065, China.
8
College of Life Sciences, Sichuan University, Chengdu 610065, China.
9
Laboratory of Department of Surgery, the First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, China.

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.

PMID:
24990744
DOI:
10.1038/nature13464
[Indexed for MEDLINE]

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