Crystal structure of bovine CD1b3 with endogenously bound ligands.

Crystal structure of bovine CD1b3 with endogenously bound ligands.
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牛CD1B3的晶体结构,具有内源结合的配体。

DOI:
10.4049/jimmunol.1000042
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发表时间:
2010-07-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Zajonc DM
Zajonc DM
中科院分区:
其他
文献类型:
--
作者:
Girardi E;Wang J;Mac TT;Versluis C;Bhowruth V;Besra G;Heck AJ;Van Rhijn I;Zajonc DM

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CD1家族的抗原提呈分子能够通过将脂类结合到连接到蛋白质表面的疏水沟槽中,将脂类展示给T细胞。特别是,CD1b亚型能够通过相互连接的疏水口袋的复杂网络与烷基链长变化很大的配体结合。有趣的是,分枝杆菌脂类,如葡萄糖单甲酸酯(GMM),专门与CD1b结合。我们测定了三种表达的牛CD1b蛋白中的一种CD1b3与内源配体形成的复合体的晶体结构,经质谱仪鉴定为磷脂酰胆碱和磷脂酰乙醇胺的混合物,并在体外分析了该蛋白与糖脂结合的能力。该结构显示了一个复杂的结合槽结构,类似于人类直系同源基因,但有相应的差异。有趣的是,在牛CD1b3中,只有A‘,C’和F‘口袋存在,而之前在人类CD1b中描述的T’口袋是关闭的。这种不同的口袋构象可能会影响boCD1b3识别具有长酰链的脂类的能力,如GMM。然而,即使在没有T‘隧道的情况下,牛CD1b3也能够在体外结合红色红球菌的分枝杆菌。
The CD1 family of antigen-presenting molecules is able to display lipids to T cells by binding them within a hydrophobic groove connected to the protein surface. In particular, the CD1b isotype is capable of binding ligands with greatly varying alkyl chain lengths through a complex network of interconnected hydrophobic pockets. Interestingly, mycobacterial lipids, such as glucose monomycolate (GMM) exclusively bind to CD1b. We determined the crystal structure of one of the three expressed bovine CD1b proteins, CD1b3, in complex with endogenous ligands, identified by mass spectrometry as a mixture of phosphatidylcholine and phosphatidylethanolamine, and analyzed the ability of the protein to bind glycolipids in vitro. The structure reveals a complex binding groove architecture, similar to the human ortholog but with consequential differences. Intriguingly, in bovine CD1b3 only the A’, C’ and F’ pockets are present while the T’ pocket previously described in human CD1b is closed. This different pocket conformation could affect the ability of boCD1b3 to recognize lipids with long acyl chains such as GMM. However, even in the absence of a T’ tunnel, bovine CD1b3 is able to bind mycolates from Rhodococcus ruber in vitro.
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