Crystal Structures of Human MD-2 and Its Complex with Antiendotoxic Lipid IVa-Reference-Cited by-同舟云学术

Crystal Structures of Human MD-2 and Its Complex with Antiendotoxic Lipid IVa

Published:2007-06-15 Issue:5831 Volume:316 Page:1632-1634
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Ohto Umeharu¹²³⁴,Fukase Koichi¹²³⁴,Miyake Kensuke¹²³⁴,Satow Yoshinori¹²³⁴

Affiliation:

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.

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 β 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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