Title : Crystal structures of human
MD-2 and its complex with antiendotoxic lipid IVa
Abstract :
- Endotoxic lipopolysaccharide (LPS) with potent immunostimulatory activity is recognized by the receptor complex of MD-2 and Toll-like receptor 4
- Crystal structures of human MD-2 and its complex with the antiendotoxic tetra-acylated lipid A core of LPS have been determined at 2.0 and 2.2 angstrom resolutions, respectively
- MD-2 shows a deep hydrophobic cavity sandwiched by two beta sheets, in which four acyl chains of the ligand are fully confined
- The phosphorylated glucosamine moieties are located at the entrance to the cavity
- These structures suggest that MD-2 plays a principal role in endotoxin recognition and provide a basis for antiseptic drug development