National Center for Protein Science Shanghai, Shanghai Science Research Center; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai, China.
National Center for Protein Science Shanghai, Shanghai Science Research Center; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai, China.
J Struct Biol. 2019 Dec 1;208(3):107384. doi: 10.1016/j.jsb.2019.09.001. Epub 2019 Sep 3.
Mannose receptor (MR, CD206) is an immune receptor highly expressed on macrophages and plays important roles in glycoprotein clearance, immune response and matrix turnover. Previous studies have shown that MR recognizes multiple ligands and recycles between cell surface and endosomes, and the conformation and ligand binding of MR are regulated by environmental pH. However, due to the lack of high-resolution details, the mechanisms of the pH-dependent properties of MR have not been fully understood. Here we investigate the pH-dependent conformational change of MR by solving a series of crystal structures of MR N-terminal fragments (CysR~CTLD2/3) at pH ranging from 4.0 to 8.5. The results show that the CTLD3 domain plays a critical role in regulating the conformational change of the N-terminal region of MR by forming interactions with the CTLD2 domain specifically at acidic pH. Moreover, the structural data also show the conformational changes of the 4-SO-GalNAc binding pocket at the CysR domain, which might be relevant to the binding and release of the ligand. Overall, these results provide a model for the pH-dependent conformational change of the N-terminal region of MR that may help to understand its functional mechanism at molecular level.
甘露糖受体（MR，CD206）是一种在巨噬细胞上高度表达的免疫受体，在糖蛋白清除、免疫反应和基质周转中发挥重要作用。先前的研究表明，MR 识别多种配体，并在细胞表面和内体之间循环，MR 的构象和配体结合受环境 pH 值的调节。然而，由于缺乏高分辨率的细节，MR 的 pH 依赖性特性的机制尚未完全理解。在这里，我们通过解决一系列在 pH 值为 4.0 到 8.5 之间的 MR N 端片段（CysR~CTLD2/3）的晶体结构来研究 MR 的 pH 依赖性构象变化。结果表明，CTLD3 结构域通过在酸性 pH 值下与 CTLD2 结构域特异性地形成相互作用，在调节 MR N 端区域的构象变化中起着关键作用。此外，结构数据还显示了 CysR 结构域上 4-SO-GalNAc 结合口袋的构象变化，这可能与配体的结合和释放有关。总体而言，这些结果为 MR N 端区域的 pH 依赖性构象变化提供了一个模型，可能有助于在分子水平上理解其功能机制。
