Secretory Immunoglobulin A (SIgA) is the most abundant antibody at the mucosal surface. It possesses two additional subunits besides IgA: the joining chain (J-chain) and secretory component (SC). SC is the ectodomain of the polymeric immunoglobulin receptor (pIgR), which functions to transport IgA to the mucosa. How the J-chain and pIgR/SC facilitate the assembly and secretion of SIgA remains incompletely understood. Furthermore, during the infection of Streptococcus pneumoniae, the pneumococcal adhesin SpsA hijacks pIgR/SC and SIgA to gain entry to human cells and evade host defense. How SpsA targets pIgR/SC and SIgA also remains elusive. Here we report a cryo-electron microscopy structure of the Fc region of IgA1 (Fcα) in complex with the J-chain and SC (Fcα-J-SC), which reveals the organization principle of SIgA. We also present a structure of Fcα-J-SC complexed with SpsA, which uncovers the specific interactions between SpsA and human pIgR/SC. These results advance the molecular understanding of SIgA and shed light on S. pneumoniae pathogenesis.

中文翻译：

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对分泌性免疫球蛋白 A 及其与肺炎球菌粘附素相互作用的结构见解。

分泌性免疫球蛋白 A (SIgA) 是黏膜表面最丰富的抗体。除了 IgA 外，它还拥有两个额外的亚基：连接链（J-chain）和分泌成分（SC）。SC 是聚合免疫球蛋白受体 (pIgR) 的胞外域，其功能是将 IgA 转运至粘膜。J 链和 pIgR/SC 如何促进 SIgA 的组装和分泌仍不完全清楚。此外，在肺炎链球菌感染期间，肺炎球菌粘附素 SpsA 会劫持 pIgR/SC 和 SIgA 以进入人体细胞并逃避宿主防御。SpsA 如何靶向 pIgR/SC 和 SIgA 仍然难以捉摸。在这里，我们报告了与 J 链和 SC (Fcα-J-SC) 复合的 IgA1 (Fcα) Fc 区的冷冻电子显微镜结构，揭示了 SIgA 的组织原理。我们还展示了与 SpsA 复合的 Fcα-J-SC 结构，它揭示了 SpsA 和人类 pIgR/SC 之间的特定相互作用。这些结果促进了对 SIgA 的分子理解并阐明了肺炎链球菌的发病机制。