Mouse mincle: characterization as a model for human mincle and evolutionary implications.
Mouse mincle: characterization as a model for human mincle and evolutionary implications.
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小鼠Mincle：表征是人类明确和进化意义的模型。
DOI：
10.3390/molecules20046670
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发表时间：
2015-04-15
期刊：
影响因子：
--
通讯作者：
Drickamer K
中科院分区：
文献类型：
--
作者：
Rambaruth ND;Jégouzo SA;Marlor H;Taylor ME;Drickamer K
Mincle是巨噬细胞诱导的c型凝集素，也被称为CLEC-4E，通过作为结核分枝杆菌和其他致病性分枝杆菌的受体，与分枝杆菌糖脂海藻糖二mycolate结合并启动信号级联反应。人类蛋白质生物学功能的研究通常依赖于小鼠模型，基于小鼠受体的生物学特性模仿人类蛋白质的假设。实验支持了这一假设，通过表达小鼠mincle的碳水化合物识别结构域和表征其与海藻糖二聚酸小分子类似物的相互作用。结果证实，小鼠微环的配体结合特性与人类受体非常相似。这些发现与在人类和奶牛中形成配体结合位点的关键氨基酸残基的保守性一致。序列比对显示，这些残基在许多哺乳动物物种中都是保守的，这表明mincle在结合配体中具有保守的功能，除了海藻糖二聚酸外，还可能包括内源性哺乳动物聚糖或病原体聚糖。
Mincle, the macrophage-inducible C-type lectin also known as CLEC-4E, binds to the mycobacterial glycolipid trehalose dimycolate and initiates a signaling cascade by serving as a receptor for Mycobacterium tuberculosis and other pathogenic mycobacterial species. Studies of the biological functions of human mincle often rely on mouse models, based on the assumption that the biological properties of the mouse receptor mimic those of the human protein. Experimental support for this assumption has been obtained by expression of the carbohydrate-recognition domain of mouse mincle and characterization of its interaction with small molecule analogs of trehalose dimycolate. The results confirm that the ligand-binding properties of mouse mincle closely parallel those of the human receptor. These findings are consistent with the conservation of key amino acid residues that have been shown to form the ligand-binding site in human and cow mincle. Sequence alignment reveals that these residues are conserved in a wide range of mammalian species, suggesting that mincle has a conserved function in binding ligands that may include endogenous mammalian glycans or pathogen glycans in addition to trehalose dimycolate.