Hefty structures of IgA and IgM complexes Immunoglobulin M (IgM) and IgA are antibody isotypes that can form higher-order secretory complexes (sIgM and sIgA), which allows them to effectively bind and neutralize antigens with low-affinity repetitive epitopes, such as those found on the surface of many bacteria and viruses. The assembly and transport of these molecules is also dependent on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR) secretory component (SC). The architecture of these complex, multimeric structures has remained elusive. Li et al. resolved cryo–electron microscopy structures of the sIgM-Fc pentamer in complex with the J-chain and SC. Using similar techniques, Kumar et al. visualized dimeric, tetrameric, and pentameric structures of secretory sIgA-Fc interacting with the J-chain and SC. Both groups report highly similar mechanisms wherein the J-chain serves as a template for antibody oligomerization. An unanticipated, amyloid-like assembly of the oligomerized structure is present in both cases, with the J-chain conferring asymmetry for pIgR binding and transcytosis. These studies may inform structure-based engineering of these molecules for future therapeutic purposes. Science, this issue p. 1014, p. 1008 Cryo–electron microscopy structures of secretory antibody multimers uncover similar organizational mechanisms. 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.

中文翻译：

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对免疫球蛋白 M 的结构洞察

IgA 和 IgM 复合物的重结构免疫球蛋白 M (IgM) 和 IgA 是抗体同种型，可以形成高级分泌复合物（sIgM 和 sIgA），这使它们能够有效地结合和中和具有低亲和力重复表位的抗原，例如那些存在于许多细菌和病毒的表面。这些分子的组装和运输也依赖于连接链（J 链）和聚合免疫球蛋白受体 (pIgR) 的分泌成分 (SC)。这些复杂的多聚体结构的架构仍然难以捉摸。李等人。解析了与 J 链和 SC 复合的 sIgM-Fc 五聚体的冷冻电子显微镜结构。使用类似的技术，Kumar 等人。与 J 链和 SC 相互作用的分泌型 sIgA-Fc 的二聚体、四聚体和五聚体结构的可视化。两组都报告了高度相似的机制，其中 J 链作为抗体寡聚化的模板。在这两种情况下都存在未预料到的淀粉样寡聚结构组装，J 链赋予 pIgR 结合和转胞吞作用的不对称性。这些研究可能会为这些分子的基于结构的工程提供信息，以用于未来的治疗目的。科学，这个问题 p。1014 页。1008 分泌性抗体多聚体的冷冻电子显微镜结构揭示了类似的组织机制。免疫球蛋白 M (IgM) 在体液免疫和粘膜免疫中都起着关键作用。它的组装和运输取决于连接链（J 链）和聚合免疫球蛋白受体 (pIgR)，但这些过程的潜在分子机制尚不清楚。我们报告了与 J 链和 pIgR 胞外域复合的人 IgM Fc 区的冷冻电子显微镜结构。IgM-Fc 五聚体是不对称形成的，类似于缺少三角形的六边形。IgM-Fc 的尾部组装成淀粉样结构以稳定五聚体。J 链覆盖尾部组件并桥接 IgM-Fc 和聚合免疫球蛋白受体之间的相互作用，后者经历了巨大的构象变化以与 IgM-J 复合物结合。这些结果为 IgM 的功能提供了结构基础。J 链覆盖尾部组件并桥接 IgM-Fc 和聚合免疫球蛋白受体之间的相互作用，后者经历了巨大的构象变化以与 IgM-J 复合物结合。这些结果为 IgM 的功能提供了结构基础。J 链覆盖尾部组件并桥接 IgM-Fc 和聚合免疫球蛋白受体之间的相互作用，后者经历了巨大的构象变化以与 IgM-J 复合物结合。这些结果为 IgM 的功能提供了结构基础。