The crystal structure of human CD1d with and without α-galactosylceramide
The crystal structure of human CD1d with and without α-galactosylceramide
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DOI：
10.1038/ni1225
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发表时间：
2005-08-01
影响因子：
30.5
通讯作者：
Cerundolo, V
中科院分区：
文献类型：
--
作者：
Koch, M;Stronge, VS;Cerundolo, V
糖脂α-半乳糖基神经酰胺以高亲和力与CD 1d结合并刺激自然杀伤T细胞。在这里，我们报告的晶体结构的人CD 1d与合成的α-半乳糖神经酰胺在3.0埃的分辨率复杂。该结构显示在CD 1d结合沟中紧密配合的脂质，鞘氨醇链结合在C'口袋中，较长的酰基链锚定在A'口袋中。我们还提出了没有脂质的CD 1d结构，其具有更开放的结合沟构象，这表明CD 1d的双重构象，其中“开放”构象更能够装载脂质。这些结构提供了关于CD 1分子如何装载糖脂的线索，以及指导新治疗剂设计的数据。
The glycolipid alpha-galactosylceramide binds with high affinity to CD1d and stimulates natural killer T cells. Here we report the crystal structure of human CD1d in complex with synthetic alpha-galactosylceramide at a resolution of 3.0 angstrom. The structure shows a tightly fit lipid in the CD1d binding groove, with the sphingosine chain bound in the C' pocket and the longer acyl chain anchored in the A' pocket. We also present the CD1d structure without lipid, which has a more open conformation of the binding groove, suggesting a dual conformation of CD1d in which the 'open' conformation is more able to load lipids. These structures provide clues as to how CD1 molecules load glycolipids as well as data to guide the design of new therapeutic agents.