Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
The Institute for AIM Medicine, Tokyo, Japan.
Nat Commun. 2024 Oct 30;15(1):9387. doi: 10.1038/s41467-024-53615-5.
Cell surface scavenger receptors contribute to homoeostasis and the response to pathogens and products associated with damage by binding to common molecular features on a wide range of targets. Apoptosis inhibitor of macrophage (AIM/CD5L) is a soluble protein belonging to the scavenger receptor cysteine-rich (SRCR) superfamily that contributes to prevention of a wide range of diseases associated with infection, inflammation, and cancer. AIM forms complexes with IgM pentamers which helps maintain high-levels of circulating AIM in serum for subsequent activation on release from the complex. The structural basis for AIM recognition of IgM as well as other binding targets is unknown. Here we apply cryogenic electron microscopy imaging (cryo-EM) to show how interfaces on both of AIM's C-terminal SRCR domains interact with the Fcμ constant region and J chain components of the IgM core. Both SRCR interfaces are also shown to contribute interactions important for AIM binding to damage-associated molecular patterns (DAMPs).
细胞表面清道夫受体通过与广泛靶标上的常见分子特征结合，有助于维持内环境平衡以及对病原体和与损伤相关产物的反应。巨噬细胞凋亡抑制剂 (AIM/CD5L) 是一种可溶性蛋白，属于清道夫受体富含半胱氨酸 (SRCR) 超家族，有助于预防与感染、炎症和癌症相关的多种疾病。AIM 与 IgM 五聚体形成复合物，有助于在从复合物中释放后保持血清中 AIM 的高水平循环，从而进行后续激活。AIM 识别 IgM 以及其他结合靶标的结构基础尚不清楚。在这里，我们应用低温电子显微镜成像 (cryo-EM) 来展示 AIM 的两个 C 末端 SRCR 结构域如何与 IgM 核心的 Fcμ 恒定区和 J 链成分相互作用。还显示这两个 SRCR 界面都有助于与损伤相关分子模式 (DAMPs) 结合的重要 AIM 相互作用。
