气候变化领域集成服务门户(CCPortal): Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab

CCPortal

DOI	10.1126/science.aba3526
	Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab
	Rougé L.; Chiang N.; Steffek M.; Kugel C.; Croll T.I.; Tam C.; Estevez A.; Arthur C.P.; Koth C.M.; Ciferri C.; Kraft E.; Payandeh J.; Nakamura G.; Koerber J.T.; Rohou A.
发表日期	2020
ISSN	0036-8075
起始页码	1224
结束页码	1230
卷号	367 期号:6483
英文摘要	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. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	CD20 antigen dimer epitope Fc receptor immunoglobulin F(ab) fragment obinutuzumab ocrelizumab ofatumumab rituximab tositumomab i 131 antibody antigen cell chemical binding composite gene expression genetic marker protein amino acid sequence antibody dependent cellular cytotoxicity antigen antibody complex antigen binding antigen structure Article cell death cell surface chemical bond complement dependent cytotoxicity drug protein binding drug targeting electron microscopy human humoral immune deficiency insect cell lipid raft malignant neoplasm molecular recognition multiple sclerosis nonhuman phagocytosis priority journal protein cross linking protein interaction stoichiometry surface plasmon resonance
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133631
推荐引用方式 GB/T 7714	Rougé L.,Chiang N.,Steffek M.,et al. Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab[J]. Science,2020,367(6483).
APA	Rougé L..,Chiang N..,Steffek M..,Kugel C..,Croll T.I..,...&Rohou A..(2020).Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.,367(6483).
MLA	Rougé L.,et al."Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab".367.6483(2020).