4N4R: Structure Basis Of Lipopolysaccharide Biogenesis

Citation:
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 beta-barrel, which is to our knowledge the largest beta-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 beta1 and beta26 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.
PDB ID: 4N4RDownload
MMDB ID: 121003
PDB Deposition Date: 2013/10/8
Updated in MMDB: 2014/07
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4N4R: dimeric; determined by author and by software (PISA)
Molecular Components in 4N4R
Label Count Molecule
Proteins (2 molecules)
1
Lps-assembly Protein Lptd(Gene symbol: imp)
Molecule annotation
1
Lps-assembly Lipoprotein Lpte(Gene symbol: rlpB)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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