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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Umeharu
authors.initials: U
authors.lastname: Ohto
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Satow
mesh_terms: 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
chemical_list: D005227:Fatty Acids; D006017:Glycolipids; C495377:LY96 protein, human; D008024:Ligands; D008050:Lipid A; D051218:Lymphocyte Antigen 96; C040142:lipid A precursors, bacterial