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Structural basis for outer membrane lipopolysaccharide insertion

DOI: 10.1038/nature13464 DOI Help
PMID: 24990744 PMID Help

Authors: Haohao Dong (Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews) , Quanju Xiang (Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews) , Yinghong Gu (Biomedical Research Centre, Norwich Medical School, University of East Anglia) , Zhongshan Wang (Biomedical Research Centre, Norwich Medical School, University of East Anglia) , Neil Paterson (Diamond Light Source) , Phillip J. Stansfeld (Department of Biochemistry, University of Oxford) , Chuan He (Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews) , Yizheng Zhang (College of Life Sciences, Sichuan University) , Wenjian Wang (Laboratory of Department of Surgery, the First Affiliated Hospital, Sun Yat-sen University) , Changjiang Dong (Biomedical Research Centre, Norwich Medical School, University of East Anglia)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature , VOL 511 (7507) , PAGES 52 - 56

State: Published (Approved)
Published: June 2014
Diamond Proposal Number(s): 7641

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.

Journal Keywords: Cell; Cell; Crystallography; X-Ray; Lipopolysaccharides; Models; Molecular; MultiProtein; Secondary; Salmonella; Structure-Activity Relationship

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 06/02/2015 10:50

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