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

被引：382

作者：

Ohto, Umeharu

Fukase, Koichi

Miyake, Kensuke

Satow, Yoshinori

机构：

[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan

[2] Osaka Univ, Grad Sch Sci, Dept Chem, Osaka 5600043, Japan

[3] Univ Tokyo, Inst Med Sci, Div Infect Genet, Minato Ku, Tokyo 1088639, Japan

[4] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan

来源：

SCIENCE | 2007年 / 316卷 / 5831期

关键词：

D O I：

10.1126/science.1139111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

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页码：1632 / 1634

页数：3

相关论文

共 29 条

[1] Lipopolysaccharide interaction with cell surface toll-like receptor 4-MD-2: Higher affinity than that with MD-2 or CD14 [J].

Akashi, S ;

Saitoh, S ;

Wakabayashi, Y ;

Kikuchi, T ;

Takamura, N ;

Nagai, Y ;

Kusumoto, Y ;

Fukase, K ;

Kusumoto, S ;

Adachi, Y ;

Kosugi, A ;

Miyake, K .

JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (07) :1035-1042

[2] Chemical structure of lipid A -: The primary immunomodulatory center of bacterial lipopolysaccharides [J].

Alexander, C ;

Zähringer, U .

TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY, 2002, 14 (76) :69-86

[3] Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care [J].

Angus, DC ;

Linde-Zwirble, WT ;

Lidicker, J ;

Clermont, G ;

Carcillo, J ;

Pinsky, MR .

CRITICAL CARE MEDICINE, 2001, 29 (07) :1303-1310

[4] Siderophore-mediated iron transport: Crystal structure of FhuA with bound lipopolysaccharide [J].

Ferguson, AD ;

Hofmann, E ;

Coulton, JW ;

Diederichs, K ;

Welte, W .

SCIENCE, 1998, 282 (5397) :2215-2220

[5] Nod-like proteins in immunity, inflammation and disease [J].

Fritz, Jorg H. ;

Ferrero, Richard L. ;

Philpott, Dana J. ;

Girardin, Stephen E. .

NATURE IMMUNOLOGY, 2006, 7 (12) :1250-1257

[6] MD-2: the Toll 'gatekeeper' in endotoxin signalling [J].

Gangloff, M ;

Gay, NJ .

TRENDS IN BIOCHEMICAL SCIENCES, 2004, 29 (06) :294-300

[7] Structural model of MD-2 and functional role of its basic amino acid clusters involved in cellular lipopolysaccharide recognition [J].

Gruber, A ;

Mancek, M ;

Wagner, H ;

Kirschning, CJ ;

Jerala, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (27) :28475-28482

[8] ML -: a conserved domain involved in innate immunity and lipid metabolism [J].

Inohara, N ;

Nuñez, G .

TRENDS IN BIOCHEMICAL SCIENCES, 2002, 27 (05) :219-221

[9] Innate immune recognition [J].

Janeway, CA ;

Medzhitov, R .

ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 :197-216

[10] Crystal structure of CD14 and its implications for lipopolysaccharide signaling [J].

Kim, JI ;

Lee, CJ ;

Jin, MS ;

Lee, CH ;

Paik, SG ;

Lee, H ;

Lee, JO .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (12) :11347-11351