美国基因泰克公司Alexis Rohou、James T. Koerber、Gerald Nakamura和Jian Payandeh合作解析分化簇20（CD20）与治疗性单克隆抗体利妥昔单抗（RTX）复合物的结构。相关论文于2020年2月20日发表在《科学》杂志上。

他们获得了CD20与RTX复合物的结构，揭示了CD20为紧密的双桶二聚体，由两个RTX抗原结合片段（Fabs）结合，每个片段都与一个复合表位和一个广泛的同型Fab：Fab界面接合。他们的数据表明RTX将CD20交联成圆形，并导致补体募集的结构模型。他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记中的潜在相关性。

据悉，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。RTX在临床上已经使用了二十年，但是如何激活补体以杀死B细胞仍然知之甚少。

附：英文原文

Title: Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab

Author: Lionel Rougé, Nancy Chiang, Micah Steffek, Christine Kugel, Tristan I. Croll, Christine Tam, Alberto Estevez, Christopher P. Arthur, Christopher M. Koth, Claudio Ciferri, Edward Kraft, Jian Payandeh, Gerald Nakamura, James T. Koerber, Alexis Rohou

Issue&Volume: 2020/02/20

Abstract: AbstractCluster of Differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and auto-immune 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 crosslinks 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.

DOI: 10.1126/science.aaz9356

Source: https://science.sciencemag.org/content/early/2020/02/19/science.aaz9356