Crystal structure of MytiLec, a galactose-binding lectin from the mussel Mytilus galloprovincialis with cytotoxicity against certain cancer cell types.
Crystal structure of MytiLec, a galactose-binding lectin from the mussel Mytilus galloprovincialis with cytotoxicity against certain cancer cell types.
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DOI：
10.1038/srep28344
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发表时间：
2016-06-20
影响因子：
4.6
通讯作者：
Tame JR
中科院分区：
文献类型：
--
作者：
Terada D;Kawai F;Noguchi H;Unzai S;Hasan I;Fujii Y;Park SY;Ozeki Y;Tame JR
MytiLec是一种从双壳贝类中分离的凝集素，对细胞表面表达三己糖基神经酰胺Galα（1，4）Galβ（1，4）Glcα1-Cer的癌细胞系具有细胞毒性活性。功能分析表明，该蛋白质与二糖蜜二糖Galα（1，6）Glc和三糖球三糖Galα（1，4）Galβ（1，4）Glc结合。在细菌中表达的重组MytiLec显示出与天然形式相同的对伯基特淋巴瘤（Raji）细胞的血细胞凝集和细胞毒性活性。晶体结构已被确定为原子分辨率，在存在和不存在配体的情况下，显示该蛋白质是β-三叶家族的成员，但具有一小群相关三叶凝集素特有的配体结合模式。单体内的三个假等价结合位点中的每一个都显示配体结合，并且蛋白质在溶液中形成紧密的二聚体。工程单体突变体失去了所有的细胞毒活性对Raji细胞，但保留了一些血凝活性，表明蛋白质的四级结构是重要的细胞效应。
MytiLec is a lectin, isolated from bivalves, with cytotoxic activity against cancer cell lines that express globotriaosyl ceramide, Galα(1,4)Galβ(1,4)Glcα1-Cer, on the cell surface. Functional analysis shows that the protein binds to the disaccharide melibiose, Galα(1,6)Glc, and the trisaccharide globotriose, Galα(1,4)Galβ(1,4)Glc. Recombinant MytiLec expressed in bacteria showed the same haemagglutinating and cytotoxic activity against Burkitt’s lymphoma (Raji) cells as the native form. The crystal structure has been determined to atomic resolution, in the presence and absence of ligands, showing the protein to be a member of the β-trefoil family, but with a mode of ligand binding unique to a small group of related trefoil lectins. Each of the three pseudo-equivalent binding sites within the monomer shows ligand binding, and the protein forms a tight dimer in solution. An engineered monomer mutant lost all cytotoxic activity against Raji cells, but retained some haemagglutination activity, showing that the quaternary structure of the protein is important for its cellular effects.