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

Cochet, F., Peri, F. (2017). The role of carbohydrates in the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) Signalling. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 18(11) [10.3390/ijms18112318].

The role of carbohydrates in the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) Signalling

Cochet, F;Peri, F.
2017

Abstract

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
Articolo in rivista - Review Essay
Kdo (3-deoxy-d-manno-octulosonic acid); Lipopolysaccharide; MD-2 (myeloid differentiation factor 2); TLR4 (toll-like receptor 4); Catalysis; Molecular Biology; Spectroscopy; Computer Science Applications1707 Computer Vision and Pattern Recognition; Physical and Theoretical Chemistry; Organic Chemistry; Inorganic Chemistry
English
2017
18
11
2318
open
Cochet, F., Peri, F. (2017). The role of carbohydrates in the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) Signalling. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 18(11) [10.3390/ijms18112318].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/180403
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