Structural Insights into the pH-Dependent Conformational Change and Collagen Recognition of the Human Mannose Receptor
Structural Insights into the pH-Dependent Conformational Change and Collagen Recognition of the Human Mannose Receptor
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DOI：
10.1016/j.str.2017.11.006
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发表时间：
2018-01-02
期刊：
影响因子：
5.7
通讯作者：
He, Yongning
中科院分区：
文献类型：
--
作者：
Hu, Zhenzheng;Shi, Xiangyi;He, Yongning
甘露糖受体（MR，CD 206）是一种存在于树突状细胞和微管上的内吞受体。它识别多种配体，在调节免疫应答和维持糖蛋白稳态中起重要作用。然而，MR的结构和功能机制仍不清楚。在这里，我们确定MR的N-末端片段的晶体结构，并揭示了胶原蛋白对纤连蛋白II结构域的潜在结合模式。SAXS和其他生物物理数据表明，MR在生理pH下采用扩展构象，并随着pH降低而发生构象变化，从而在酸性环境中形成紧凑构象。此外，生化数据表明，MR结合胶原蛋白在生理pH值的Ca 2+增强的方式，而Ca 2+在酸性pH值的结合没有影响。这些结果提供了一个模型的MR关于其配体的结合和释放过程中细胞表面和内体之间的回收的动态机制。
Mannose receptor (MR, CD206) is an endocytic receptor on microphages and dendritic cells. It recognizes multiple ligands and plays important roles in regulating immune responses and maintaining glycoprotein homeostasis. However, the structure and functional mechanism of MR remain unclear. Here we determine the crystal structures of the N-terminal fragments of MR and reveal the potential binding mode of collagen on the fibronectin II domain. The SAXS and other biophysical data suggest that MR adopts an extended conformation at physiological pH and undergoes conformational changes as pH decreases, resulting in a compact conformation in an acidic environment. Moreover, biochemical data show that MR binds to collagen in a Ca2+-enhanced manner at physiological pH, whereas Ca2+ has no effect on the binding at acidic pH. These results provide a model for the dynamic mechanism of MR regarding its ligand binding and release during the recycling between cell surface and endosomes.