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The molecular basis of the host response to lipopolysaccharide

Nature Reviews Microbiology volume 8, pages 8–14 (2010)Cite this article

Abstract

Lipopolysaccharide (LPS), which is produced by Gram-negative bacteria, is a powerful activator of innate immune responses. LPS binds to the proteins Toll-like receptor 4 (TLR4) and MD2 to activate pro-inflammatory signalling pathways. The TLR4–MD2 receptor complex is crucial for the host recognition of Gram-negative bacterial infection, and pathogens have devised many strategies to evade or manipulate TLR4–MD2 activity. The TLR4–MD2 signalling pathway is therefore potentially an important therapeutic target. This Progress article focuses on recent exciting data that have revealed the structural basis of TLR4–MD2 recognition of LPS.

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Figure 1: Lipid A structures.
Figure 2: MD2 and Toll-like receptor crystal structures.
Figure 3: Docking model of MAL and TRAM binding at the Toll-like receptor 4 homodimer interface.

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Acknowledgements

We would like to thank the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the Wellcome Trust and the Horserace Betting Levy Board for funding our work. We apologise to those authors whose work we were unable to cite owing to space constraints.

Author information

Authors and Affiliations

  1. Clare E. Bryant is at the Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 OES, UK.,

    Clare E. Bryant

  2. David R. Spring is at the Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.,

    David R. Spring

  3. Monique Gangloff and Nicholas J. Gay are at the Department of Biochemistry, University of Cambridge, 80 Tennis Court Road Cambridge, CB2 1GA, UK.,

    Monique Gangloff & Nicholas J. Gay

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  1. Clare E. Bryant
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  2. David R. Spring
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Correspondence to Clare E. Bryant.

Supplementary information

Supplementary information S1 (figure)

The structures of lipid A from different bacterial species and the structures of synthetic lipid A analogues. (PDF 175 kb)

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DATABASES

Entrez Genome

mouse mammary tumour virus

Entrez Genome Project

Brucella melitensis

Chlamydia pneumoniae

Escherichia coli

Paracoccus denitrificans

Porphyromonas gingivalis

Pseudomonas aeruginosa

Rhodobacter sphaeroides

Salmonella enterica subsp. enterica serovar Enteritidis

Streptococcus pneumoniae

Yersinia pestis

Protein Data Bank

2E59

2Z65

2Z7X

3CIY

3FXI

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Bryant, C., Spring, D., Gangloff, M. et al. The molecular basis of the host response to lipopolysaccharide. Nat Rev Microbiol 8, 8–14 (2010). https://doi.org/10.1038/nrmicro2266

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