Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
NCBI PubMed ID: 21924775Publication DOI: 10.1016/j.molimm.2011.08.003Journal NLM ID: 7905289Publisher: Elsevier
Correspondence: M.L. DeMarco <mdemarco
wustl.edu>; R.J. Woods <rwoods
ccrc.uga.edu>
Institutions: Complex Carbohydrate Research Center, 315 Riverbend Road, University of Georgia, 30602, USA
The human immune response to an infection by Gram-negative bacteria involves detection of lipopolysaccharides (LPS), also known as endotoxins, which comprise the bacterial outer cell wall. Distinct from mammalian glycolipid structures, LPS have a conserved chemical pattern that is recognized by the pattern recognition receptor complex formed by myeloid differentiation protein 2 (MD-2) and toll-like receptor 4 (TLR4). A remarkable immune-mediated structure-toxicity relationship has been defined that relates to the number of acyl chains in the endotoxin. While there is a clear correlation between endotoxin acylation and elicited agonist or antagonist responses, the 3D structural basis of this relationship remains unclear. In order to explore, at atomic-resolution, the effects of a range of chemically distinct endotoxins on the structure and dynamics of their MD-2.endotoxin complexes, we examined a series of variably acylated lipid A molecules from Escherichia coli and Neisseria meningitidis in complex with human MD-2. Through the application of molecular dynamics simulations, in concert with experimental data, we have identified specific structural and dynamic features of the MD-2-endotoxin complexes that may control dimerization of TLR4 molecules. As dimerization is central to the release of downstream chemical mediators, the results provide a structural foundation for the ability of endotoxins to act as either agonists or antagonists of the TLR4 pathway.
Lipopolysaccharide, lipid A, endotoxin, TLR4, molecular dynamics simulations, MD-2
Structure type: oligomer
Location inside paper: p.125, fig.2(a) E. coli
Compound class: lipid A
Contained glycoepitopes: IEDB_141806,IEDB_142488,IEDB_144998,IEDB_145002,IEDB_146664,IEDB_176772,IEDB_534864,IEDB_983931,SB_192
Methods: MD simulations, modeling
3D data: 3D data
Related record ID(s): 31980
NCBI Taxonomy refs (TaxIDs): 562
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