Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa

Science. 2007 Jun 15;316(5831):1632-4. doi: 10.1126/science.1139111.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Fatty Acids / chemistry
  • Glycolipids / chemistry*
  • Glycolipids / metabolism
  • Glycosylation
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Ligands
  • Lipid A / analogs & derivatives*
  • Lipid A / chemistry
  • Lipid A / metabolism
  • Lymphocyte Antigen 96 / chemistry*
  • Lymphocyte Antigen 96 / metabolism
  • Models, Molecular
  • Phosphorylation
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary


  • Fatty Acids
  • Glycolipids
  • LY96 protein, human
  • Ligands
  • Lipid A
  • Lymphocyte Antigen 96
  • lipid A precursors, bacterial

Associated data

  • PDB/2E56
  • PDB/2E59