Molecular basis of sugar recognition by the human L-type lectins ERGIC-53, VIPL, and VIP36
Molecular basis of sugar recognition by the human L-type lectins ERGIC-53, VIPL, and VIP36
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DOI：
10.1074/jbc.m709384200
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发表时间：
2008-01-25
影响因子：
4.8
通讯作者：
Kato, Koichi
中科院分区：
文献类型：
--
作者：
Kamiya, Yukiko;Kamiya, Daiki;Kato, Koichi
ERGIC-53、VIPL和VIP 36是哺乳动物早期分泌途径的相关1型膜蛋白。它们被归类为L型凝集素，因为它们的管腔糖识别结构域，表现出与豆科凝集素的同源性。这些L-型凝集素在分泌途径的内质网-高尔基体系统中具有不同的细胞内分布和动力学，并且以Ca 2+依赖的方式与糖蛋白的N-聚糖相互作用，表明在糖蛋白分选和运输中的作用。为了理解这些凝集素的功能，了解它们的碳水化合物特异性是至关重要的，但仅可用于VIP 36（Kamiya，Y.，Yamaguchi，Y.，Takahashi，N.，阿拉塔，Y.，加塞，K.一、Ihara，Y.，松尾岛伊藤，Y.，Yamamoto，K.，Kato，K.（2005）J.Biol.Chem.280，37178-37182）。在这里，我们提供了一个全面的和定量的糖识别ERGIC-53和VIPL的碳水化合物识别结构域的糖识别与VIP 36相比，使用吡啶胺化的糖库结合正面亲和色谱分析。正面亲和层析揭示了VIPL和VIP 36与高甘露糖型寡糖的D1分支中的去葡萄糖基化三甘露糖的选择性相互作用，但具有不同的pH依赖性。ERGIC-53以低亲和力和广泛特异性结合高甘露糖型寡糖，不能区分单葡萄糖基化和去葡萄糖基化高甘露糖型寡糖。基于结合这些蛋白质的已知功能的糖结合特性，我们提出了一个模型的糖蛋白的指导和贩运的三个凝集素的行动。此外，基于结构的诱变显示，这些L-型凝集素的糖结合特性可以通过单个氨基酸取代来切换。
ERGIC-53, VIPL, and VIP36 are related type 1 membrane proteins of the mammalian early secretory pathway. They are classified as L-type lectins because of their luminal carbohydrate recognition domain, which exhibits homology to leguminous lectins. These L-type lectins have different intracellular distributions and dynamics in the endoplasmic reticulum-Golgi system of the secretory pathway and interact with N-glycans of glycoproteins in a Ca2+ -dependent manner, suggesting a role in glycoprotein sorting and trafficking. To understand the function of these lectins, knowledge of their carbohydrate specificity is crucial but only available for VIP36 (Kamiya, Y., Yamaguchi, Y., Takahashi, N., Arata, Y., Kasai, K. I., Ihara, Y., Matsuo, I., Ito, Y., Yamamoto, K., and Kato, K. ( 2005) J. Biol. Chem. 280, 37178-37182). Here we provide a comprehensive and quantitative analysis of sugar recognition of the carbohydrate recognition domains of ERGIC-53 and VIPL in comparison with VIP36 using a pyridylaminated sugar library in conjunction with frontal affinity chromatography. Frontal affinity chromatography revealed selective interaction of VIPL and VIP36 with the deglucosylated trimannose in the D1 branch of high-mannose-type oligosaccharides but with different pH dependence. ERGIC-53 bound high-mannose-type oligosaccharides with low affinity and broad specificity, not discriminating between monoglucosylated and deglucosylated high-mannose-type oligosaccharides. Based on the sugar-binding properties in conjunction with known features of these proteins, we propose a model for the action of the three lectins in glycoprotein guidance and trafficking. Moreover, structure-based mutagenesis revealed that the sugar-binding properties of these L-type lectins can be switched by single amino acid substitutions.