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Endotoxic lipopolysaccharide (LPS) with potent immunostimulatoryactivity is recognized by the receptor complex of MD-2 and Toll-likereceptor 4. Crystal structures of human MD-2 and its complexwith the antiendotoxic tetra-acylated lipid A core of LPS havebeen determined at 2.0 and 2.2 angstrom resolutions, respectively.MD-2 shows a deep hydrophobic cavity sandwiched by two ßsheets, in which four acyl chains of the ligand are fully confined.The phosphorylated glucosamine moieties are located at the entranceto the cavity. These structures suggest that MD-2 plays a principalrole in endotoxin recognition and provide a basis for antisepticdrug development.
1 Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. 2 Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan. 3 Division of Infectious Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. 4 CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
* To whom correspondence should be addressed. E-mail: satowy{at}mol.f.u-tokyo.ac.jp
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