Structural basis for outer membrane lipopolysaccharide insertion

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. 52-6. ISSN 0028-0836

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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:	Article
Uncontrolled Keywords:	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
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User:	Pure Connector
Date Deposited:	17 Nov 2014 12:58
Last Modified:	20 Mar 2024 00:59
URI:	https://ueaeprints.uea.ac.uk/id/eprint/50980
DOI:	10.1038/nature13464

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