The cryo-EM structure of the endocytic receptor DEC-205.
The cryo-EM structure of the endocytic receptor DEC-205.
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DOI：
10.1074/jbc.ra120.016451
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Berry R
中科院分区：
文献类型：
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作者：
Gully BS;Venugopal H;Fulcher AJ;Fu Z;Li J;Deuss FA;Llerena C;Heath WR;Lahoud MH;Caminschi I;Rossjohn J;Berry R
DEC-205（CD 205）是巨噬细胞甘露糖受体蛋白家族的成员，是树突状细胞的原型内吞受体，其配体包括硫代磷酸化胞嘧啶-鸟苷寡核苷酸，这是细菌或病毒DNA中常见的基序。然而，尽管越来越多的生物学和临床意义，很少有人知道这种受体或其任何家庭成员的结构安排。在这里，我们描述了人DEC-205的3.2 kDa冷冻电镜结构，从而阐明了甘露糖受体蛋白家族的结构。DEC-205单体形成包含C型凝集素样结构域的两个插入环的紧凑结构，其中N-末端富含半胱氨酸的结构域和纤连蛋白结构域位于中心交叉点。我们使用基于溶液的技术建立了形成四聚体DEC-205的pH依赖性寡聚化途径，并最终解析了DEC-205四聚体的4.9 μ mol/L cryo-EM结构，以鉴定能够形成四聚体的第二凝集素环的展开。此外，我们建议的相关性，这种寡聚化途径内的细胞设置，从而胞嘧啶-鸟苷结合出现破坏这种细胞表面寡聚体。因此，我们提供了深入了解DEC-205受体的结构和寡聚体组装。
DEC-205 (CD205), a member of the macrophage mannose receptor protein family, is the prototypic endocytic receptor of dendritic cells, whose ligands include phosphorothioated cytosine–guanosine oligonucleotides, a motif often seen in bacterial or viral DNA. However, despite growing biological and clinical significance, little is known about the structural arrangement of this receptor or any of its family members. Here, we describe the 3.2 Å cryo-EM structure of human DEC-205, thereby illuminating the structure of the mannose receptor protein family. The DEC-205 monomer forms a compact structure comprising two intercalated rings of C-type lectin-like domains, where the N-terminal cysteine-rich and fibronectin domains reside at the central intersection. We establish a pH-dependent oligomerization pathway forming tetrameric DEC-205 using solution-based techniques and ultimately solved the 4.9 Å cryo-EM structure of the DEC-205 tetramer to identify the unfurling of the second lectin ring which enables tetramer formation. Furthermore, we suggest the relevance of this oligomerization pathway within a cellular setting, whereby cytosine–guanosine binding appeared to disrupt this cell-surface oligomer. Accordingly, we provide insight into the structure and oligomeric assembly of the DEC-205 receptor.