State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Science. 2020 Feb 28;367(6481):1014-1017. doi: 10.1126/science.aaz5425. Epub 2020 Feb 6.
Immunoglobulin M (IgM) plays a pivotal role in both humoral and mucosal immunity. Its assembly and transport depend on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR), but the underlying molecular mechanisms of these processes are unclear. We report a cryo-electron microscopy structure of the Fc region of human IgM in complex with the J-chain and pIgR ectodomain. The IgM-Fc pentamer is formed asymmetrically, resembling a hexagon with a missing triangle. The tailpieces of IgM-Fc pack into an amyloid-like structure to stabilize the pentamer. The J-chain caps the tailpiece assembly and bridges the interaction between IgM-Fc and the polymeric immunoglobulin receptor, which undergoes a large conformational change to engage the IgM-J complex. These results provide a structural basis for the function of IgM.
免疫球蛋白 M（IgM）在体液免疫和黏膜免疫中都起着关键作用。它的组装和运输依赖于连接链（J 链）和多聚免疫球蛋白受体（pIgR），但这些过程的潜在分子机制尚不清楚。我们报告了人 IgM 的 Fc 区域与 J 链和 pIgR 胞外域复合物的低温电子显微镜结构。IgM-Fc 五聚体不对称形成，类似于一个缺少三角形的六边形。IgM-Fc 的尾部片段形成淀粉样结构以稳定五聚体。J 链覆盖尾部组装并桥接 IgM-Fc 与多聚免疫球蛋白受体之间的相互作用，后者发生大的构象变化以与 IgM-J 复合物结合。这些结果为 IgM 的功能提供了结构基础。
