Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa
Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa
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DOI：
10.1126/science.1139111
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发表时间：
2007-06-15
期刊：
影响因子：
56.9
通讯作者：
Satow, Yoshinori
中科院分区：
文献类型：
--
作者：
Ohto, Umeharu;Fukase, Koichi;Satow, Yoshinori
内毒素脂多糖（LPS）具有强烈的免疫刺激活性，被MD-2和Toll样受体4的受体复合物识别。已分别在2.0和2.2埃分辨率下测定了人MD-2及其与LPS的抗内毒素四酰化脂质A核心的复合物的晶体结构。MD-2显示了夹在两个β片层之间的深疏水空腔，其中配体的四个酰基链被完全限制。磷酸化葡糖胺部分位于腔的入口处。这些结构表明MD-2在内毒素识别中起主要作用，并为抗菌药物的开发提供了基础。
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.