4N4R

Structure basis of lipopolysaccharide biogenesis

Summary for 4N4R

• Entry DOI: 10.2210/pdb4n4r/pdb
• Descriptor: LPS-assembly protein LptD, LPS-assembly lipoprotein LptE, CACODYLATE ION, ... (5 entities in total)
• Functional Keywords: beta barrel, translocase, lipopolysaccharide transport proteins, membrane protein
• Biological source: Salmonella enterica subsp. enterica serovar Typhimurium; More
• Cellular location: Cell outer membrane (By similarity): Q8ZRW0; Cell outer membrane; Lipid-anchor (By similarity): Q8ZQZ7
• Total number of polymer chains: 4
• Total formula weight: 225816.46

Authors

Dong, H.,Xiang, Q.,Wang, Z.,Paterson, N.G.,He, C.,Zhang, Y.,Wang, W.,Dong, C. (deposition date: 2013-10-08, release date: 2014-06-25, Last modification date: 2024-11-20)

Primary citation

Dong, H.,Xiang, Q.,Gu, Y.,Wang, Z.,Paterson, N.G.,Stansfeld, P.J.,He, C.,Zhang, Y.,Wang, W.,Dong, C.
Structural basis for outer membrane lipopolysaccharide insertion.
Nature, 511:52-56, 2014

PubMed 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.

PubMed: 24990744
DOI: 10.1038/nature13464

Experimental method

X-RAY DIFFRACTION (2.8 Å)