| Literature DB >> 32079680 |
Lionel Rougé1, Nancy Chiang2, Micah Steffek3, Christine Kugel4, Tristan I Croll5, Christine Tam4, Alberto Estevez1, Christopher P Arthur1, Christopher M Koth1, Claudio Ciferri1, Edward Kraft4, Jian Payandeh6,2, Gerald Nakamura7, James T Koerber7, Alexis Rohou6.
Abstract
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.Entities:
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Year: 2020 PMID： 32079680 DOI： 10.1126/science.aaz9356
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728