Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa.
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.
Ohto
Umeharu
U
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Fukase
Koichi
K
Miyake
Kensuke
K
Satow
Yoshinori
Y
D001665:Binding Sites; D018360:Crystallography, X-Ray; D005227:Fatty Acids / Q000737:chemistry; D006017:Glycolipids / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008050:Lipid A / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D051218:Lymphocyte Antigen 96 / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010766:Phosphorylation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary
D005227:Fatty Acids; D006017:Glycolipids; C495377:LY96 protein, human; D008024:Ligands; D008050:Lipid A; D051218:Lymphocyte Antigen 96; C040142:lipid A precursors, bacterial