Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
NCBI PubMed ID: 29099761Publication DOI: 10.3390/ijms18112318Journal NLM ID: 101092791Publisher: Basel, Switzerland: MDPI
Correspondence: f.cochet
campus.unimib.it; rancesco.peri
unimib.it
Institutions: Department of Biotechnology and Biosciences, University of Milano Bicocca, Piazza della Scienza, 2, 20126 Milano, Italy
The interactions between sugar-containing molecules from the bacteria cell wall and pattern recognition receptors (PRR) on the plasma membrane or cytosol of specialized host cells are the first molecular events required for the activation of higher animal's immune response and inflammation. This review focuses on the role of carbohydrates of bacterial endotoxin (lipopolysaccharide, LPS, lipooligosaccharide, LOS, and lipid A), in the interaction with the host Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD-2) complex. The lipid chains and the phosphorylated disaccharide core of lipid A moiety are responsible for the TLR4 agonist action of LPS, and the specific interaction between MD-2, TLR4, and lipid A are key to the formation of the activated complex (TLR4/MD-2/LPS)₂, which starts intracellular signalling leading to nuclear factors activation and to production of inflammatory cytokines. Subtle chemical variations in the lipid and sugar parts of lipid A cause dramatic changes in endotoxin activity and are also responsible for the switch from TLR4 agonism to antagonism. While the lipid A pharmacophore has been studied in detail and its structure-activity relationship is known, the contribution of core saccharides 3-deoxy-d-manno-octulosonic acid (Kdo) and heptosyl-2-keto-3-deoxy-octulosonate (Hep) to TLR4/MD-2 binding and activation by LPS and LOS has been investigated less extensively. This review focuses on the role of lipid A, but also of Kdo and Hep sugars in LPS/TLR4 signalling.
Lipopolysaccharide, TLR4 (Toll-like receptor 4), MD-2 (myeloid differentiation factor 2), Kdo (3-deoxy-d-manno-octulosonic acid)
Structure type: oligomer
Location inside paper: fig.3 E. coli
Trivial name: lipid IVA
Compound class: LOS, lipid A, glycolipid
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_176772,IEDB_534864
Comments, role: review
Related record ID(s): 11996, 12336, 12337, 12339, 12340, 12341, 12342
NCBI Taxonomy refs (TaxIDs): 562Reference(s) to other database(s): GlycomeDB:
7396
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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