Characterization of sugar binding by the mannose receptor family member, Endo180
Characterization of sugar binding by the mannose receptor family member, Endo180
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DOI：
10.1074/jbc.m208985200
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发表时间：
2002-12-27
影响因子：
4.8
通讯作者：
Isacke, CM
中科院分区：
文献类型：
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作者：
East, L;Rushton, S;Isacke, CM
甘露糖受体家族的成员包括甘露糖受体、磷脂酶A(2)受体、DEC-205和Endo180，它们在一个多肽中含有多个C型凝集素样域(CTLD)。此外，在它们的N端，所有四个家族成员都含有一个富含半胱氨酸的结构域，类似于蓖麻毒素的R型碳水化合物识别结构域。然而，尽管普遍存在多个凝集素样结构域，但这四个内源性受体具有不同的配体结合活性，显然这些结构域中的大多数不与糖结合。在这里，我们研究了最近发现的家族成员Endo180的凝集素样结构域的功能。Endo180与甘露糖、岩藻糖和N-乙酰氨基葡萄糖结合依赖于钙离子，但不与半乳糖结合。这种活性是由八种CTLDs之一CTLD2介导的。竞争分析表明，Endo180 CTLD2的单糖结合专一性与甘露糖受体CTLD4相似。然而，更多的实验表明，与甘露糖受体的富含半胱氨酸的区域不同，Endo180的富含半胱氨酸的区域并不结合硫酸盐糖。因此，虽然现在已知Endo180和甘露糖受体都是甘露糖结合凝集素，但在体内每个受体可能都有一组不同的糖蛋白配体。
Members of the mannose receptor family, the mannose receptor, the phospholipase A(2) receptor, DEC-205, and Endo180, contain multiple C-type lectin-like domains (CTLDs) within a single polypeptide. In addition, at their N termini, all four family members contain a cysteine-rich domain similar to the R-type carbohydrate recognition domains of ricin. However, despite the common presence of multiple lectin-like domains, these four endocytic receptors have divergent ligand binding activities, and it is clear that the majority of these domains do not bind sugars. Here the functions of the lectin-like domains of the most recently discovered family member, Endo180, have been investigated. Endo180 is shown to bind in a Ca2+-dependent manner to mannose, fucose, and N-acetylglucosamine but not to galactose. This activity is mediated by one of the eight CTLDs, CTLD2. Competition assays indicate that the monosaccharide binding specificity of Endo180 CTLD2 is similar to that of mannose receptor CTLD4. However, additional experiments indicate that, unlike the cysteine-rich domain of the mannose receptor, the cysteine-rich domain of Endo180 does not bind sulfated sugars. Thus, although Endo180 and the mannose receptor are now both known to be mannose binding lectins, each receptor is likely to have a distinct set of glycoprotein ligands in vivo.