Clustering for the kill Cluster of differentiation 20 (CD20) is a membrane protein that defines most B cell populations and is the target of therapeutic antibodies to treat malignancies and autoimmune disorders. Rougé et al. present the structure of CD20 bound to the antibody rituximab that activates the complement system to kill B cells. CD20 forms a dimer and each monomer binds one rituximab antigen-binding fragment (Fab) to give 2:2 stoichiometry. The compact packing between Fab arms and CD20 gives rise to circular assemblies with a diameter similar to that of antibody hexamers known to recruit the first component of the complement cascade. Science, this issue p. 1224 The cryo–electron microscopy structure of a CD20-rituximab complex explains how the antibody helps promote B cell killing. Cluster of differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and autoimmune disorders but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX cross-links CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers.

中文翻译：

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CD20 与治疗性单克隆抗体利妥昔单抗复合物的结构

分化簇 20 (CD20) 是一种定义大多数 B 细胞群的膜蛋白，是治疗恶性肿瘤和自身免疫性疾病的治疗性抗体的靶标。胭脂等。呈现与抗体利妥昔单抗结合的 CD20 结构，该抗体可激活补体系统以杀死 B 细胞。CD20 形成二聚体，每个单体与一个利妥昔单抗抗原结合片段 (Fab) 结合，化学计量比为 2:2。Fab 臂和 CD20 之间的紧密堆积产生了圆形组件，其直径类似于已知募集补体级联第一组分的抗体六聚体的直径。科学，这个问题 p。1224 CD20-利妥昔单抗复合物的冷冻电子显微镜结构解释了抗体如何帮助促进 B 细胞杀伤。分化簇 20 (CD20) 是一种 B 细胞膜蛋白，被单克隆抗体靶向用于治疗恶性肿瘤和自身免疫性疾病，但其结构和功能未知。利妥昔单抗 (RTX) 已在临床上使用了二十年，但它如何激活补体以杀死 B 细胞仍知之甚少。我们获得了与 RTX 复合的 CD20 结构，揭示 CD20 是一个紧凑的双桶二聚体，由两个 RTX 抗原结合片段 (Fab) 结合，每个片段都与复合表位和广泛的同型 Fab:Fab 界面结合。我们的数据表明 RTX 将 CD20 交联成圆形组件并导致补体募集的结构模型。我们的结果进一步强调了同型 Fab:Fab 相互作用在靶向寡聚细胞表面标志物方面的潜在相关性。