Structure of human CD1b with bound ligands at 2.3 Å, a maze for alkyl chains
Structure of human CD1b with bound ligands at 2.3 Å, a maze for alkyl chains
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DOI：
10.1038/ni821
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发表时间：
2002-08-01
影响因子：
30.5
通讯作者：
Cerundolo, V
中科院分区：
文献类型：
--
作者：
Gadola, SD;Zaccai, NR;Cerundolo, V
人类基因组编码5种非多态性主要组织相容性复合体I类糖蛋白，CD 1a至CD 1 e，其呈递脂质抗原以供T淋巴细胞特异性识别。使用单烷基链洗涤剂，我们开发了一个协议，以产生重组人CD 1b-脂质复合物。我们在这里提出的晶体结构的CD 1b的复合物与磷脂酰肌醇或神经节苷脂GM 2在2.3埃和2.8埃的分辨率，分别。抗原结合沟容纳四个互连的疏水通道，其被糖脂的烷基链加上两个去污剂分子占据。在2螺旋下方的明显出口进一步有助于结合凹槽的可塑性。这些结构揭示了两个烷基链脂质与CD 1b结合的机制，以及CD 1b如何适应不同烷基链长度的配体。他们还建议如何非常长的烷基链，如分枝菌酸，可以完全包含在结合槽。这些结果扩展了潜在的CD 1b配体的光谱，揭示了除了两个烷基链脂质，单烷基和三烷基链脂质可以容纳在结合沟。
The human genome encodes five nonpolymorphic major histocompatibility complex class I-like glycoproteins, CD1a to CD1e, that present lipid antigens for specific recognition by T lymphocytes. Using single alkyl chain detergents, we developed a protocol to generate recombinant human CD1b-lipid complexes. We present here the crystal structures of CD1b in complex with either phosphatidylinositol or ganglioside GM2 at 2.3 Angstrom and 2.8 Angstrom resolutions, respectively. The antigen-binding groove houses four interlinked hydrophobic channels that are occupied by the alkyl chains of the glycolipid plus two detergent molecules. A distinct exit beneath the 2 helix further contributes to the plasticity of the binding groove. These structures reveal the mechanism by which two alkyl chain lipids bind to CD1b, and how CD1b can adapt to ligands of different alkyl chain length. They also suggest how very long alkyl chains, such as those of mycolic acid, could be fully contained within the binding groove. These results extend the spectrum of potential CD1b ligands by revealing that, in addition to two alkyl chain lipids, mono-alkyl and triple-alkyl chain lipids can be accommodated in the binding groove.